chr10-71362188-T-C

Position:

chr10-71362188-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018344.6(SLC29A3):c.1008T>C(p.Gly336Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,613,930 control chromosomes in the GnomAD database, including 633,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54089 hom., cov: 31)

Exomes 𝑓: 0.89 ( 579237 hom. )

Consequence

SLC29A3
NM_018344.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 0.338

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-71362188-T-C is Benign according to our data. Variant chr10-71362188-T-C is described in ClinVar as [Benign]. Clinvar id is 130337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71362188-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.338 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.91 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.1008T>C	p.Gly336Gly	synonymous_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.1008T>C	p.Gly336Gly	synonymous_variant	6/6	1	NM_018344.6	ENSP00000362285.5		Q9BZD2-1

Frequencies

GnomAD3 genomes

AF:

0.839

AC:

127430

AN:

151934

Hom.:

54069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.756

Gnomad AMI

AF:

0.996

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.945

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.752

Gnomad FIN

AF:

0.837

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.916

Gnomad OTH

AF:

0.856

GnomAD3 exomes

AF:

0.825

AC:

207364

AN:

251278

Hom.:

87290

AF XY:

0.835

AC XY:

113444

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.754

Gnomad AMR exome

AF:

0.626

Gnomad ASJ exome

AF:

0.946

Gnomad EAS exome

AF:

0.723

Gnomad SAS exome

AF:

0.773

Gnomad FIN exome

AF:

0.837

Gnomad NFE exome

AF:

0.912

Gnomad OTH exome

AF:

0.860

GnomAD4 exome

AF:

0.887

AC:

1296561

AN:

1461878

Hom.:

579237

Cov.:

AF XY:

0.886

AC XY:

644087

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.749

Gnomad4 AMR exome

AF:

0.633

Gnomad4 ASJ exome

AF:

0.944

Gnomad4 EAS exome

AF:

0.715

Gnomad4 SAS exome

AF:

0.779

Gnomad4 FIN exome

AF:

0.844

Gnomad4 NFE exome

AF:

0.917

Gnomad4 OTH exome

AF:

0.882

GnomAD4 genome

AF:

0.839

AC:

127501

AN:

152052

Hom.:

54089

Cov.:

AF XY:

0.831

AC XY:

61762

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.756

Gnomad4 AMR

AF:

0.748

Gnomad4 ASJ

AF:

0.945

Gnomad4 EAS

AF:

0.723

Gnomad4 SAS

AF:

0.752

Gnomad4 FIN

AF:

0.837

Gnomad4 NFE

AF:

0.916

Gnomad4 OTH

AF:

0.853

Alfa

AF:

0.900

Hom.:

93158

Bravo

AF:

0.827

Asia WGS

AF:

0.684

AC:

2383

AN:

3478

EpiCase

AF:

0.922

EpiControl

AF:

0.921

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 16, 2020	- -
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. -

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 89% of patients studied by a panel of primary immunodeficiencies. Number of patients: 85. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.0

DANN

Benign

0.49

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