rs780668

Variant names:

Variant summary

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

The NM_018344.6(SLC29A3):c.473C>T(p.Ser158Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.701 in 1,613,958 control chromosomes in the GnomAD database, including 409,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,drug response (★★).

Frequency

Genomes: 𝑓 0.61 ( 31114 hom., cov: 32)

Exomes 𝑓: 0.71 ( 378130 hom. )

Consequence

SLC29A3
NM_018344.6 missense

Scores

Clinical Significance

Benign; drug response criteria provided, multiple submitters, no conflicts B:7O:3

Conservation

PhyloP100: 7.50

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:

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=3.6845643E-6).

BP6

Variant 10-71351651-C-T is Benign according to our data. Variant chr10-71351651-C-T is described in ClinVar as [Benign, drug_response]. Clinvar id is 130341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71351651-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC29A3	NM_018344.6 link	c.473C>T	p.Ser158Phe	missense_variant	Exon 4 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.473C>T	p.Ser158Phe	missense_variant	Exon 4 of 6	1	NM_018344.6	ENSP00000362285.5		Q9BZD2-1

Frequencies

GnomAD3 genomes

AF:

0.613

AC:

93188

AN:

151976

Hom.:

31124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.923

Gnomad AMR

AF:

0.587

Gnomad ASJ

AF:

0.736

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.741

Gnomad MID

AF:

0.697

Gnomad NFE

AF:

0.760

Gnomad OTH

AF:

0.645

GnomAD3 exomes

AF:

0.639

AC:

160758

AN:

251472

Hom.:

54270

AF XY:

0.650

AC XY:

88296

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.352

Gnomad AMR exome

AF:

0.485

Gnomad ASJ exome

AF:

0.733

Gnomad EAS exome

AF:

0.456

Gnomad SAS exome

AF:

0.530

Gnomad FIN exome

AF:

0.741

Gnomad NFE exome

AF:

0.755

Gnomad OTH exome

AF:

0.697

GnomAD4 exome

AF:

0.711

AC:

1038771

AN:

1461864

Hom.:

378130

Cov.:

AF XY:

0.708

AC XY:

514870

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.492

Gnomad4 ASJ exome

AF:

0.734

Gnomad4 EAS exome

AF:

0.364

Gnomad4 SAS exome

AF:

0.539

Gnomad4 FIN exome

AF:

0.744

Gnomad4 NFE exome

AF:

0.755

Gnomad4 OTH exome

AF:

0.689

GnomAD4 genome

AF:

0.613

AC:

93189

AN:

152094

Hom.:

31114

Cov.:

AF XY:

0.610

AC XY:

45321

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.362

Gnomad4 AMR

AF:

0.586

Gnomad4 ASJ

AF:

0.736

Gnomad4 EAS

AF:

0.428

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.741

Gnomad4 NFE

AF:

0.760

Gnomad4 OTH

AF:

0.643

Alfa

AF:

0.717

Hom.:

83919

Bravo

AF:

0.588

TwinsUK

AF:

0.746

AC:

2766

ALSPAC

AF:

0.752

AC:

2900

ESP6500AA

AF:

0.367

AC:

1615

ESP6500EA

AF:

0.747

AC:

6426

ExAC

AF:

0.638

AC:

77492

Asia WGS

AF:

0.460

AC:

1602

AN:

3478

EpiCase

AF:

0.756

EpiControl

AF:

0.759

ClinVar

Significance: Benign; drug response

Submissions summary: Benign:7Other:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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	Eurofins Ntd Llc (ga)	Sep 11, 2018	- -
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 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported. -

H syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

not provided

Benign:1Other:1

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	Jun 09, 2021	This variant is associated with the following publications: (PMID: 28842327) -

Gemcitabine response

Other:1

drug response, criteria provided, single submitter

research

Bioinformatics Institute, Agency for Science, Technology and Research

Jan 01, 2017

- correlated with patient outcome with gemcitabine-based chemotherpy

Acanthosis nigricans

Other:1

association, no assertion criteria provided

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Mutations in this gene can predispose to acanthosis nigricans in patients with insulin dependent diabetes. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

.;D;D

MetaRNN

Benign

0.0000037

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

3.1

M;M;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.3

.;D;.

REVEL

Benign

0.29

Sift

Benign

0.062

.;T;.

Polyphen

0.66

P;P;.

Vest4

0.31

MPC

0.39

ClinPred

0.064

GERP RS

4.6

Varity_R

0.30

gMVP

0.61

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