NM_001372327.1:c.442G>T

Variant names:

• chr6-44230034-G-T
• rs61758844
• NM_001372327.1:c.442G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001372327.1(SLC29A1):​c.442G>T​(p.Val148Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000809 in 1,607,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V148M) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: SLC29A1 NM_001372327.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14675695).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372327.1. 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
	SLC29A1	NM_001372327.1	MANE Select	c.442G>T	p.Val148Leu	missense	Exon 5 of 13	NP_001359256.1	Q99808-1
	SLC29A1	NM_001304462.2		c.679G>T	p.Val227Leu	missense	Exon 6 of 14	NP_001291391.1	Q99808-2
	SLC29A1	NM_001304465.2		c.520G>T	p.Val174Leu	missense	Exon 5 of 13	NP_001291394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A1	ENST00000371755.9	TSL:1 MANE Select	c.442G>T	p.Val148Leu	missense	Exon 5 of 13	ENSP00000360820.3	Q99808-1
	SLC29A1	ENST00000371708.1	TSL:1	c.442G>T	p.Val148Leu	missense	Exon 4 of 12	ENSP00000360773.1	Q99808-1
	SLC29A1	ENST00000393844.7	TSL:1	c.442G>T	p.Val148Leu	missense	Exon 5 of 13	ENSP00000377427.1	Q99808-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 246878 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000756 AC: 11 AN: 1455424 Hom.: 0 Cov.: 35 AF XY: 0.00000690 AC XY: 5 AN XY: 724254

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111970

Other (OTH) AF: 0.0000331 AC: 2 AN: 60344

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000184 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.085	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.073
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.33
Sift	Benign	0.66	T
Sift4G	Benign	1.0	T
Polyphen		0.0070	B
Vest4		0.36
MVP		0.50
MPC		0.26
ClinPred		0.090	T
GERP RS		-4.4
Varity_R		0.16
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs61758844; hg19: chr6-44197771;