chr11-66366466-G-C

Position:

• chr11-66366466-G-C

Variant summary

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

The NM_001532.3(SLC29A2):​c.832C>G​(p.Pro278Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC29A2 NM_001532.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.890

Genes affected

SLC29A2 (HGNC:11004): (solute carrier family 29 member 2) The uptake of nucleosides by transporters, such as SLC29A2, is essential for nucleotide synthesis by salvage pathways in cells that lack de novo biosynthetic pathways. Nucleoside transport also plays a key role in the regulation of many physiologic processes through its effect on adenosine concentration at the cell surface (Griffiths et al., 1997 [PubMed 9396714]).[supplied by OMIM, Nov 2008]

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=0.07446161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC29A2	NM_001532.3	c.832C>G	p.Pro278Ala	missense_variant	8/12	ENST00000357440.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC29A2	ENST00000357440.7	c.832C>G	p.Pro278Ala	missense_variant	8/12	1	NM_001532.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.832C>G (p.P278A) alteration is located in exon 8 (coding exon 8) of the SLC29A2 gene. This alteration results from a C to G substitution at nucleotide position 832, causing the proline (P) at amino acid position 278 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.8
DANN	Benign	0.60
DEOGEN2	Benign	0.090	T;T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.61	.;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L;L
MutationTaster	Benign	0.98	D;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.61	N;N;N
REVEL	Benign	0.098
Sift	Benign	0.43	T;T;T
Sift4G	Benign	0.49	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.21
MutPred		0.35		Loss of glycosylation at P278 (P = 0.0276);Loss of glycosylation at P278 (P = 0.0276);Loss of glycosylation at P278 (P = 0.0276);
MVP		0.42
MPC		0.12
ClinPred		0.27	T
GERP RS		4.3
Varity_R		0.032
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-66133937;