rs2252996

Variant names:

• chr10-71356185-G-A
• rs2252996
• NM_018344.6:c.715G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-71356185-G-A
• chr10-71356185-G-C
• chr10-71356185-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018344.6(SLC29A3):​c.715G>A​(p.Val239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,613,592 control chromosomes in the GnomAD database, including 606,088 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. V239V) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.84 (54379 hom., cov: 32)
  • Exomes 𝑓: 0.87 (551709 hom.)
• Consequence: SLC29A3 NM_018344.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.160
• Publications: 40 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.0462653E-7).
• BP6: Variant 10-71356185-G-A is Benign according to our data. Variant chr10-71356185-G-A is described in ClinVar as Benign. ClinVar VariationId is 130344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 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.715G>A	p.Val239Ile	missense	Exon 5 of 6	NP_060814.4
	SLC29A3	NM_001363518.2		c.481G>A	p.Val161Ile	missense	Exon 5 of 6	NP_001350447.1	A0A2R8YDR8
	SLC29A3	NM_001174098.2		c.715G>A	p.Val239Ile	missense	Exon 5 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.715G>A	p.Val239Ile	missense	Exon 5 of 6	ENSP00000362285.5	Q9BZD2-1
	SLC29A3	ENST00000479577.2	TSL:2	c.481G>A	p.Val161Ile	missense	Exon 5 of 6	ENSP00000493995.1	A0A2R8YDR8
	SLC29A3	ENST00000469204.1	TSL:2	n.206G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.843 AC: 127916 AN: 151700 Hom.: 54373 Cov.: 32

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.865

GnomAD2 exomes AF: 0.818 AC: 205690 AN: 251338 AF XY: 0.826

Gnomad AFR exome AF: 0.811

Gnomad AMR exome AF: 0.642

Gnomad ASJ exome AF: 0.937

Gnomad EAS exome AF: 0.687

Gnomad FIN exome AF: 0.864

Gnomad NFE exome AF: 0.885

Gnomad OTH exome AF: 0.857

GnomAD4 exome AF: 0.866 AC: 1266087 AN: 1461776 Hom.: 551709 Cov.: 64 AF XY: 0.865 AC XY: 629144 AN XY: 727188

African (AFR) AF: 0.818 AC: 27394 AN: 33478

American (AMR) AF: 0.648 AC: 28975 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 24445 AN: 26136

East Asian (EAS) AF: 0.652 AC: 25874 AN: 39698

South Asian (SAS) AF: 0.781 AC: 67406 AN: 86258

European-Finnish (FIN) AF: 0.865 AC: 46168 AN: 53376

Middle Eastern (MID) AF: 0.909 AC: 5244 AN: 5768

European-Non Finnish (NFE) AF: 0.889 AC: 988212 AN: 1111958

Other (OTH) AF: 0.867 AC: 52369 AN: 60388

GnomAD4 genome AF: 0.843 AC: 127968 AN: 151816 Hom.: 54379 Cov.: 32 AF XY: 0.840 AC XY: 62294 AN XY: 74180

African (AFR) AF: 0.814 AC: 33711 AN: 41434

American (AMR) AF: 0.749 AC: 11439 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3252 AN: 3468

East Asian (EAS) AF: 0.677 AC: 3460 AN: 5110

South Asian (SAS) AF: 0.766 AC: 3696 AN: 4822

European-Finnish (FIN) AF: 0.866 AC: 9124 AN: 10530

Middle Eastern (MID) AF: 0.884 AC: 258 AN: 292

European-Non Finnish (NFE) AF: 0.889 AC: 60306 AN: 67860

Other (OTH) AF: 0.861 AC: 1814 AN: 2106

Alfa AF: 0.871 Hom.: 223496

Bravo AF: 0.832

TwinsUK AF: 0.882 AC: 3269

ALSPAC AF: 0.883 AC: 3404

ESP6500AA AF: 0.809 AC: 3563

ESP6500EA AF: 0.889 AC: 7643

ExAC AF: 0.822 AC: 99742

Asia WGS AF: 0.694 AC: 2416 AN: 3478

EpiCase AF: 0.896

EpiControl AF: 0.897

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	H syndrome (3)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.0080
DANN	Benign	0.74
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	7.0e-7	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.16
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.12
Sift	Benign	0.51	T
Polyphen		0.0020	B
Vest4		0.049
MPC		0.061
ClinPred		0.0077	T
GERP RS		-2.2
Varity_R		0.0098
gMVP		0.15

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: rs2252996; hg19: chr10-73115942; COSMIC: COSV104427495;