rs2487068

Positions:

chr10-71362156-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.976A>G(p.Ile326Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 1,613,932 control chromosomes in the GnomAD database, including 600,978 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 0.87 ( 57523 hom., cov: 30)

Exomes 𝑓: 0.86 ( 543455 hom. )

Consequence

SLC29A3
NM_018344.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -0.576

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=9.737729E-7).

BP6

Variant 10-71362156-A-G is Benign according to our data. Variant chr10-71362156-A-G is described in ClinVar as [Benign]. Clinvar id is 130347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71362156-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 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.976A>G	p.Ile326Val	missense_variant	6/6	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.976A>G	p.Ile326Val	missense_variant	6/6	1	NM_018344.6	ENSP00000362285.5		Q9BZD2-1

Frequencies

GnomAD3 genomes

AF:

0.866

AC:

131570

AN:

151944

Hom.:

57479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.926

Gnomad AMI

AF:

0.989

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.885

Gnomad EAS

AF:

0.705

Gnomad SAS

AF:

0.769

Gnomad FIN

AF:

0.855

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.875

Gnomad OTH

AF:

0.868

GnomAD3 exomes

AF:

0.819

AC:

205805

AN:

251350

Hom.:

85516

AF XY:

0.824

AC XY:

111972

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.927

Gnomad AMR exome

AF:

0.641

Gnomad ASJ exome

AF:

0.889

Gnomad EAS exome

AF:

0.713

Gnomad SAS exome

AF:

0.779

Gnomad FIN exome

AF:

0.856

Gnomad NFE exome

AF:

0.871

Gnomad OTH exome

AF:

0.841

GnomAD4 exome

AF:

0.860

AC:

1257180

AN:

1461870

Hom.:

543455

Cov.:

AF XY:

0.858

AC XY:

624306

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.926

Gnomad4 AMR exome

AF:

0.646

Gnomad4 ASJ exome

AF:

0.882

Gnomad4 EAS exome

AF:

0.678

Gnomad4 SAS exome

AF:

0.786

Gnomad4 FIN exome

AF:

0.859

Gnomad4 NFE exome

AF:

0.878

Gnomad4 OTH exome

AF:

0.865

GnomAD4 genome

AF:

0.866

AC:

131669

AN:

152062

Hom.:

57523

Cov.:

AF XY:

0.862

AC XY:

64025

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.926

Gnomad4 AMR

AF:

0.745

Gnomad4 ASJ

AF:

0.885

Gnomad4 EAS

AF:

0.705

Gnomad4 SAS

AF:

0.769

Gnomad4 FIN

AF:

0.855

Gnomad4 NFE

AF:

0.875

Gnomad4 OTH

AF:

0.865

Alfa

AF:

0.866

Hom.:

119921

Bravo

AF:

0.860

TwinsUK

AF:

0.871

AC:

3230

ALSPAC

AF:

0.873

AC:

3364

ESP6500AA

AF:

0.922

AC:

4062

ESP6500EA

AF:

0.877

AC:

7543

ExAC

AF:

0.825

AC:

100108

Asia WGS

AF:

0.702

AC:

2445

AN:

3478

EpiCase

AF:

0.876

EpiControl

AF:

0.876

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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 92% of patients studied by a panel of primary immunodeficiencies. Number of patients: 88. Only high quality variants are reported. -

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 provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 16, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.0010

DANN

Benign

0.36

DEOGEN2

Benign

0.013

T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.37

.;T;T

MetaRNN

Benign

9.7e-7

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.52

N;N;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.080

.;N;.

REVEL

Benign

0.027

Sift

Benign

1.0

.;T;.

Polyphen

0.0020

B;B;.

Vest4

0.012

MPC

0.053

ClinPred

0.021

GERP RS

-9.0

Varity_R

0.027

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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