6-44223649-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001372327.1(SLC29A1):c.-52+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,202,240 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (8 hom.)
• Consequence: SLC29A1 NM_001372327.1 splice_region, intron
• Scores: Splicing: ADA: 0.00007013
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.920

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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 6-44223649-C-T is Benign according to our data. Variant chr6-44223649-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3040920.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 400 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC29A1	NM_001372327.1	c.-52+8C>T		splice_region_variant, intron_variant		ENST00000371755.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC29A1	ENST00000371755.9	c.-52+8C>T		splice_region_variant, intron_variant		1	NM_001372327.1	P1

Frequencies

GnomAD3 genomes AF: 0.00263 AC: 400 AN: 152010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00500

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00230 AC: 165 AN: 71726 Hom.: 0 AF XY: 0.00218 AC XY: 90 AN XY: 41286

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000632

Gnomad FIN exome AF: 0.00136

Gnomad NFE exome AF: 0.00572

Gnomad OTH exome AF: 0.00243

GnomAD4 exome AF: 0.00438 AC: 4599 AN: 1050122 Hom.: 8 Cov.: 32 AF XY: 0.00426 AC XY: 2186 AN XY: 513522

Gnomad4 AFR exome AF: 0.000612

Gnomad4 AMR exome AF: 0.000168

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000907

Gnomad4 FIN exome AF: 0.00257

Gnomad4 NFE exome AF: 0.00509

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.00264 AC: 401 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.00198 AC XY: 147 AN XY: 74376

Gnomad4 AFR AF: 0.000819

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00502

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00376 Hom.: 0

Bravo AF: 0.00250

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC29A1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 30, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.1
Dann	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000070
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.030		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: rs748411158; hg19: chr6-44191386;