chr6-44232346-G-T

Variant names:

• chr6-44232346-G-T
• rs747025115
• NM_001372327.1:c.977G>T

Variant summary

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

The NM_001372327.1(SLC29A1):​c.977G>T​(p.Arg326Leu) 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. 16/20 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: not found (cov: 32)
• Consequence: SLC29A1 NM_001372327.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

Genes affected

SLC29A1 (HGNC:11003): (solute carrier family 29 member 1 (Augustine blood group)) This gene is a member of the equilibrative nucleoside transporter family. The gene encodes a transmembrane glycoprotein that localizes to the plasma and mitochondrial membranes and mediates the cellular uptake of nucleosides from the surrounding medium. The protein is categorized as an equilibrative (as opposed to concentrative) transporter that is sensitive to inhibition by nitrobenzylthioinosine (NBMPR). Nucleoside transporters are required for nucleotide synthesis in cells that lack de novo nucleoside synthesis pathways, and are also necessary for the uptake of cytotoxic nucleosides used for cancer and viral chemotherapies. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 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=0.10649946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC29A1	NM_001372327.1	c.977G>T	p.Arg326Leu	missense_variant	Exon 11 of 13	ENST00000371755.9	NP_001359256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC29A1	ENST00000371755.9	c.977G>T	p.Arg326Leu	missense_variant	Exon 11 of 13	1	NM_001372327.1	ENSP00000360820.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.8
DANN	Benign	0.91
DEOGEN2	Benign	0.10	T;T;T;T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.83	T;.;.;.;.;.
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;N;N;N;N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.75	N;N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.36	T;T;T;T;T;T
Sift4G	Benign	0.33	T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;B
Vest4		0.21
MVP		0.093
ClinPred		0.072	T
GERP RS		0.18
Varity_R		0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs747025115; hg19: chr6-44200083;