rs16928737

Positions:

• chr10-71351775-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000373189.6(SLC29A3):​c.597G>A​(p.Gln199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00663 in 1,612,488 control chromosomes in the GnomAD database, including 517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (269 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (248 hom.)
• Consequence: SLC29A3 ENST00000373189.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.58

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 10-71351775-G-A is Benign according to our data. Variant chr10-71351775-G-A is described in ClinVar as [Benign]. Clinvar id is 130336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71351775-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC29A3	NM_018344.6	c.597G>A	p.Gln199=	synonymous_variant	4/6	ENST00000373189.6	NP_060814.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC29A3	ENST00000373189.6	c.597G>A	p.Gln199=	synonymous_variant	4/6	1	NM_018344.6	ENSP00000362285	P1

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4991 AN: 152124 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.00937 AC: 2333 AN: 248864 Hom.: 114 AF XY: 0.00708 AC XY: 954 AN XY: 134658

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.00868

Gnomad ASJ exome AF: 0.00398

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000658

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000956

Gnomad OTH exome AF: 0.00820

GnomAD4 exome AF: 0.00390 AC: 5692 AN: 1460246 Hom.: 248 Cov.: 35 AF XY: 0.00349 AC XY: 2534 AN XY: 726380

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.00952

Gnomad4 ASJ exome AF: 0.00364

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000696

Gnomad4 OTH exome AF: 0.00896

GnomAD4 genome AF: 0.0328 AC: 4995 AN: 152242 Hom.: 269 Cov.: 32 AF XY: 0.0311 AC XY: 2313 AN XY: 74438

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000911

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0156 Hom.: 74

Bravo AF: 0.0381

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.00155

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

H syndrome Benign:2

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	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 05, 2013

- -

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
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.0
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs16928737; hg19: chr10-73111532;