rs16928737

Variant names:

• chr10-71351775-G-A
• rs16928737
• NM_018344.6:c.597G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018344.6(SLC29A3):​c.597G>A​(p.Gln199Gln) 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 NM_018344.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.58
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• H syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
• dysosteosclerosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 130336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018344.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	NM_018344.6	MANE Select	c.597G>A	p.Gln199Gln	synonymous	Exon 4 of 6	NP_060814.4
	SLC29A3	NM_001363518.2		c.363G>A	p.Gln121Gln	synonymous	Exon 4 of 6	NP_001350447.1	A0A2R8YDR8
	SLC29A3	NM_001174098.2		c.597G>A	p.Gln199Gln	synonymous	Exon 4 of 6	NP_001167569.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	ENST00000373189.6	TSL:1 MANE Select	c.597G>A	p.Gln199Gln	synonymous	Exon 4 of 6	ENSP00000362285.5	Q9BZD2-1
	SLC29A3	ENST00000479577.2	TSL:2	c.363G>A	p.Gln121Gln	synonymous	Exon 4 of 6	ENSP00000493995.1	A0A2R8YDR8
	SLC29A3	ENST00000469204.1	TSL:2	n.88G>A		non_coding_transcript_exon	Exon 1 of 3

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

GnomAD2 exomes AF: 0.00937 AC: 2333 AN: 248864 AF XY: 0.00708

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 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

African (AFR) AF: 0.113 AC: 3796 AN: 33464

American (AMR) AF: 0.00952 AC: 425 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00364 AC: 95 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86156

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52228

Middle Eastern (MID) AF: 0.00728 AC: 42 AN: 5768

European-Non Finnish (NFE) AF: 0.000696 AC: 774 AN: 1111796

Other (OTH) AF: 0.00896 AC: 541 AN: 60380

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

African (AFR) AF: 0.112 AC: 4652 AN: 41514

American (AMR) AF: 0.0137 AC: 210 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000911 AC: 62 AN: 68020

Other (OTH) AF: 0.0241 AC: 51 AN: 2116

Alfa AF: 0.0171 Hom.: 84

Bravo AF: 0.0381

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.00155

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	H syndrome (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.0
DANN	Benign	0.52
PhyloP100		2.6

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

Other links and lift over

dbSNP: rs16928737; hg19: chr10-73111532;