6-44225969-C-G

Variant names:

• chr6-44225969-C-G
• rs731780
• NM_001372327.1:c.-51-1294C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372327.1(SLC29A1):​c.-51-1294C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 231,858 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.023 (122 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (10 hom.)
• Consequence: SLC29A1 NM_001372327.1 intron
• Scores: Splicing: ADA: 0.00002255
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A1	NM_001372327.1	MANE Select	c.-51-1294C>G		intron	N/A	NP_001359256.1
	SLC29A1	NM_001304462.2		c.187-1294C>G		intron	N/A	NP_001291391.1
	SLC29A1	NM_001304465.2		c.25-1291C>G		intron	N/A	NP_001291394.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A1	ENST00000371755.9	TSL:1 MANE Select	c.-51-1294C>G		intron	N/A	ENSP00000360820.3
	SLC29A1	ENST00000393844.7	TSL:1	c.-51-1294C>G		intron	N/A	ENSP00000377427.1
	SLC29A1	ENST00000371740.10	TSL:1	c.-158-92C>G		intron	N/A	ENSP00000360805.6

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3541 AN: 152112 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00771

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00212 AC: 169 AN: 79628 Hom.: 10 Cov.: 1 AF XY: 0.00195 AC XY: 75 AN XY: 38378

African (AFR) AF: 0.101 AC: 147 AN: 1456

American (AMR) AF: 0.00 AC: 0 AN: 72

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 494

East Asian (EAS) AF: 0.0101 AC: 3 AN: 298

South Asian (SAS) AF: 0.00126 AC: 2 AN: 1592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22

Middle Eastern (MID) AF: 0.0116 AC: 2 AN: 172

European-Non Finnish (NFE) AF: 0.0000960 AC: 7 AN: 72920

Other (OTH) AF: 0.00307 AC: 8 AN: 2602

GnomAD4 genome AF: 0.0234 AC: 3557 AN: 152230 Hom.: 122 Cov.: 32 AF XY: 0.0229 AC XY: 1703 AN XY: 74440

African (AFR) AF: 0.0792 AC: 3289 AN: 41510

American (AMR) AF: 0.00889 AC: 136 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00812 AC: 42 AN: 5174

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68008

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.0179 Hom.: 14

Bravo AF: 0.0270

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.33
DANN	Benign	0.73
PhyloP100		-0.99
PromoterAI		0.031	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.040		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: rs731780; hg19: chr6-44193706;