rs2277257

Positions:

chr10-71322806-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018344.6(SLC29A3):c.52A>G(p.Arg18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,876 control chromosomes in the GnomAD database, including 147,529 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17987 hom., cov: 33)

Exomes 𝑓: 0.42 ( 129542 hom. )

Consequence

SLC29A3
NM_018344.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.472

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 links:

SLC29A3 (HGNC:):

SLC29A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.353772E-6).

BP6

Variant 10-71322806-A-G is Benign according to our data. Variant chr10-71322806-A-G is described in ClinVar as [Benign]. Clinvar id is 130342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC29A3	NM_018344.6 linkuse as main transcript	c.52A>G	p.Arg18Gly	missense_variant	2/6	ENST00000373189.6	NP_060814.4	Q9BZD2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC29A3	ENST00000373189.6 linkuse as main transcript	c.52A>G	p.Arg18Gly	missense_variant	2/6	1	NM_018344.6	ENSP00000362285.5		Q9BZD2-1

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

71954

AN:

151934

Hom.:

17977

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.451

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.445

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.440

GnomAD3 exomes

AF:

0.415

AC:

103688

AN:

249644

Hom.:

22353

AF XY:

0.416

AC XY:

56224

AN XY:

135104

show subpopulations

Gnomad AFR exome

AF:

0.649

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.432

Gnomad EAS exome

AF:

0.339

Gnomad SAS exome

AF:

0.453

Gnomad FIN exome

AF:

0.441

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.404

GnomAD4 exome

AF:

0.417

AC:

610001

AN:

1461824

Hom.:

129542

Cov.:

AF XY:

0.417

AC XY:

303470

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.653

Gnomad4 AMR exome

AF:

0.311

Gnomad4 ASJ exome

AF:

0.427

Gnomad4 EAS exome

AF:

0.361

Gnomad4 SAS exome

AF:

0.452

Gnomad4 FIN exome

AF:

0.442

Gnomad4 NFE exome

AF:

0.412

Gnomad4 OTH exome

AF:

0.428

GnomAD4 genome

AF:

0.474

AC:

72003

AN:

152052

Hom.:

17987

Cov.:

AF XY:

0.473

AC XY:

35120

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.645

Gnomad4 AMR

AF:

0.382

Gnomad4 ASJ

AF:

0.446

Gnomad4 EAS

AF:

0.352

Gnomad4 SAS

AF:

0.455

Gnomad4 FIN

AF:

0.445

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.439

Alfa

AF:

0.411

Hom.:

26835

Bravo

AF:

0.470

TwinsUK

AF:

0.417

AC:

1548

ALSPAC

AF:

0.418

AC:

1610

ESP6500AA

AF:

0.636

AC:

2802

ESP6500EA

AF:

0.411

AC:

3537

ExAC

AF:

0.424

AC:

51537

Asia WGS

AF:

0.422

AC:

1467

AN:

3478

EpiCase

AF:

0.394

EpiControl

AF:

0.400

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

H syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 49. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.58

.;T

MetaRNN

Benign

0.0000034

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.050

Sift

Benign

0.11

.;T

Polyphen

0.0010

B;B

Vest4

0.066

MPC

0.075

ClinPred

0.0030

GERP RS

1.2

Varity_R

0.078

gMVP

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over