rs2252996

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018344.6(SLC29A3):c.715G>A(p.Val239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,613,592 control chromosomes in the GnomAD database, including 606,088 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. V239V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.84 ( 54379 hom., cov: 32)

Exomes 𝑓: 0.87 ( 551709 hom. )

Consequence

SLC29A3
NM_018344.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.160

Publications

40 publications found

Variant links:

Genes affected

SLC29A3 (HGNC:23096): (solute carrier family 29 member 3) This gene encodes a nucleoside transporter. The encoded protein plays a role in cellular uptake of nucleosides, nucleobases, and their related analogs. Mutations in this gene have been associated with H syndrome, which is characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism. A related disorder, PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus), has also been associated with mutations at this locus. Alternatively spliced transcript variants have been described.[provided by RefSeq, Mar 2010]

SLC29A3 Gene-Disease associations (from GenCC):

H syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
dysosteosclerosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC29A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.0462653E-7).

BP6

Variant 10-71356185-G-A is Benign according to our data. Variant chr10-71356185-G-A is described in ClinVar as Benign. ClinVar VariationId is 130344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC29A3	NM_018344.6 link	c.715G>A	p.Val239Ile	missense_variant	Exon 5 of 6	ENST00000373189.6	NP_060814.4	Q9BZD2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC29A3	ENST00000373189.6 link	c.715G>A	p.Val239Ile	missense_variant	Exon 5 of 6	1	NM_018344.6	ENSP00000362285.5		Q9BZD2-1

Frequencies

GnomAD3 genomes

AF:

0.843

AC:

127916

AN:

151700

Hom.:

54373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.814

Gnomad AMI

AF:

0.996

Gnomad AMR

AF:

0.749

Gnomad ASJ

AF:

0.938

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.767

Gnomad FIN

AF:

0.866

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.889

Gnomad OTH

AF:

0.865

GnomAD2 exomes

AF:

0.818

AC:

205690

AN:

251338

AF XY:

0.826

show subpopulations

Gnomad AFR exome

AF:

0.811

Gnomad AMR exome

AF:

0.642

Gnomad ASJ exome

AF:

0.937

Gnomad EAS exome

AF:

0.687

Gnomad FIN exome

AF:

0.864

Gnomad NFE exome

AF:

0.885

Gnomad OTH exome

AF:

0.857

GnomAD4 exome

AF:

0.866

AC:

1266087

AN:

1461776

Hom.:

551709

Cov.:

AF XY:

0.865

AC XY:

629144

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.818

AC:

27394

AN:

33478

American (AMR)

AF:

0.648

AC:

28975

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.935

AC:

24445

AN:

26136

East Asian (EAS)

AF:

0.652

AC:

25874

AN:

39698

South Asian (SAS)

AF:

0.781

AC:

67406

AN:

86258

European-Finnish (FIN)

AF:

0.865

AC:

46168

AN:

53376

Middle Eastern (MID)

AF:

0.909

AC:

5244

AN:

5768

European-Non Finnish (NFE)

AF:

0.889

AC:

988212

AN:

1111958

Other (OTH)

AF:

0.867

AC:

52369

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

9767

19534

29300

39067

48834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21300

42600

63900

85200

106500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.843

AC:

127968

AN:

151816

Hom.:

54379

Cov.:

AF XY:

0.840

AC XY:

62294

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.814

AC:

33711

AN:

41434

American (AMR)

AF:

0.749

AC:

11439

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.938

AC:

3252

AN:

3468

East Asian (EAS)

AF:

0.677

AC:

3460

AN:

5110

South Asian (SAS)

AF:

0.766

AC:

3696

AN:

4822

European-Finnish (FIN)

AF:

0.866

AC:

9124

AN:

10530

Middle Eastern (MID)

AF:

0.884

AC:

258

AN:

292

European-Non Finnish (NFE)

AF:

0.889

AC:

60306

AN:

67860

Other (OTH)

AF:

0.861

AC:

1814

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1009

2017

3026

4034

5043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.871

Hom.:

223496

Bravo

AF:

0.832

TwinsUK

AF:

0.882

AC:

3269

ALSPAC

AF:

0.883

AC:

3404

ESP6500AA

AF:

0.809

AC:

3563

ESP6500EA

AF:

0.889

AC:

7643

ExAC

AF:

0.822

AC:

99742

Asia WGS

AF:

0.694

AC:

2416

AN:

3478

EpiCase

AF:

0.896

EpiControl

AF:

0.897

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

H syndrome

Benign:3

May 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 94% of patients studied by a panel of primary immunodeficiencies. Number of patients: 90. Only high quality variants are reported. -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Oct 21, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.0080

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.011

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.33

.;T;T

MetaRNN

Benign

7.0e-7

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;L;.

PhyloP100

0.16

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.19

.;N;.

REVEL

Benign

0.12

Sift

Benign

0.51

.;T;.

Polyphen

0.0020

B;B;.

Vest4

0.049

MPC

0.061

ClinPred

0.0077

GERP RS

-2.2

Varity_R

0.0098

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over