NM_018344.6:c.1008T>C

Variant names:

• chr10-71362188-T-C
• rs1084004
• NM_018344.6:c.1008T>C

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: 0.338
• Publications: 30 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=-0.88).
• BP6: Variant 10-71362188-T-C is Benign according to our data. Variant chr10-71362188-T-C is described in ClinVar as Benign. ClinVar VariationId is 130337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.1008T>C	p.Gly336Gly	synonymous	Exon 6 of 6	NP_060814.4
	SLC29A3	NM_001363518.2		c.774T>C	p.Gly258Gly	synonymous	Exon 6 of 6	NP_001350447.1	A0A2R8YDR8
	SLC29A3	NM_001174098.2		c.*237T>C		3_prime_UTR	Exon 6 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.1008T>C	p.Gly336Gly	synonymous	Exon 6 of 6	ENSP00000362285.5	Q9BZD2-1
	SLC29A3	ENST00000479577.2	TSL:2	c.774T>C	p.Gly258Gly	synonymous	Exon 6 of 6	ENSP00000493995.1	A0A2R8YDR8
	SLC29A3	ENST00000469204.1	TSL:2	n.505T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127430 AN: 151934 Hom.: 54069 Cov.: 31

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

GnomAD2 exomes AF: 0.825 AC: 207364 AN: 251278 AF XY: 0.835

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 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.: 82 AF XY: 0.886 AC XY: 644087 AN XY: 727238

African (AFR) AF: 0.749 AC: 25087 AN: 33480

American (AMR) AF: 0.633 AC: 28325 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 24661 AN: 26136

East Asian (EAS) AF: 0.715 AC: 28367 AN: 39700

South Asian (SAS) AF: 0.779 AC: 67179 AN: 86258

European-Finnish (FIN) AF: 0.844 AC: 45062 AN: 53414

Middle Eastern (MID) AF: 0.920 AC: 5304 AN: 5768

European-Non Finnish (NFE) AF: 0.917 AC: 1019314 AN: 1112004

Other (OTH) AF: 0.882 AC: 53262 AN: 60396

GnomAD4 genome AF: 0.839 AC: 127501 AN: 152052 Hom.: 54089 Cov.: 31 AF XY: 0.831 AC XY: 61762 AN XY: 74304

African (AFR) AF: 0.756 AC: 31332 AN: 41460

American (AMR) AF: 0.748 AC: 11413 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 3279 AN: 3470

East Asian (EAS) AF: 0.723 AC: 3727 AN: 5152

South Asian (SAS) AF: 0.752 AC: 3617 AN: 4810

European-Finnish (FIN) AF: 0.837 AC: 8851 AN: 10580

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62311 AN: 68000

Other (OTH) AF: 0.853 AC: 1802 AN: 2112

Alfa AF: 0.890 Hom.: 201816

Bravo AF: 0.827

Asia WGS AF: 0.684 AC: 2383 AN: 3478

EpiCase AF: 0.922

EpiControl AF: 0.921

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.49
PhyloP100		0.34

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: rs1084004; hg19: chr10-73121945; COSMIC: COSV64385266; COSMIC: COSV64385266;