chr10-71322775-C-G

Variant names:

• chr10-71322775-C-G
• rs746298917
• NM_018344.6:c.21C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018344.6(SLC29A3):​c.21C>G​(p.Asp7Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: SLC29A3 NM_018344.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13022703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC29A3	NM_018344.6	c.21C>G	p.Asp7Glu	missense_variant	Exon 2 of 6	ENST00000373189.6	NP_060814.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC29A3	ENST00000373189.6	c.21C>G	p.Asp7Glu	missense_variant	Exon 2 of 6	1	NM_018344.6	ENSP00000362285.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74356

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.025
DANN	Benign	0.92
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.49	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.0	.;N
REVEL	Benign	0.12
Sift	Benign	0.032	.;D
Polyphen		1.0	D;D
Vest4		0.12
MutPred		0.22		Gain of phosphorylation at S12 (P = 0.2277);Gain of phosphorylation at S12 (P = 0.2277);
MVP		0.66
MPC		0.061
ClinPred		0.46	T
GERP RS		-1.9
Varity_R		0.061
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs746298917; hg19: chr10-73082532;