rs324148

Positions:

• chr6-44228841-T-C

Variant summary

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

The NM_001372327.1(SLC29A1):​c.30-549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,236 control chromosomes in the GnomAD database, including 46,901 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 0.78 (46901 hom., cov: 34)
• Consequence: SLC29A1 NM_001372327.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC29A1	NM_001372327.1	c.30-549T>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.30-549T>C		intron_variant		1	NM_001372327.1	ENSP00000360820.3

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118845 AN: 152118 Hom.: 46846 Cov.: 34

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.797

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.781 AC: 118954 AN: 152236 Hom.: 46901 Cov.: 34 AF XY: 0.782 AC XY: 58190 AN XY: 74442

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.795

Alfa AF: 0.744 Hom.: 57713

Bravo AF: 0.785

Asia WGS AF: 0.742 AC: 2581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.57

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: rs324148; hg19: chr6-44196578;