rs1128930

Positions:

• chr6-44232588-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372327.1(SLC29A1):​c.1059+160A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 644,174 control chromosomes in the GnomAD database, including 35,685 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 0.32 (7986 hom., cov: 33)
  • Exomes 𝑓: 0.33 (27699 hom.)
• Consequence: SLC29A1 NM_001372327.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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]

POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

SLC29A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC29A1	NM_001372327.1	c.1059+160A>C		intron_variant		ENST00000371755.9	NP_001359256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC29A1	ENST00000371755.9	c.1059+160A>C		intron_variant		1	NM_001372327.1	ENSP00000360820.3

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48405 AN: 152066 Hom.: 7979 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.328 AC: 161588 AN: 491990 Hom.: 27699 Cov.: 5 AF XY: 0.323 AC XY: 84679 AN XY: 262096

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.318 AC: 48438 AN: 152184 Hom.: 7986 Cov.: 33 AF XY: 0.319 AC XY: 23725 AN XY: 74388

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.356

Alfa AF: 0.343 Hom.: 1097

Bravo AF: 0.310

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.036
DANN	Benign	0.62

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: rs1128930; hg19: chr6-44200325; COSMIC: COSV57581098; COSMIC: COSV57581098;