Variant chr6-44223649-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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 (no stars).

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 no assertion criteria provided B:1

Conservation

PhyloP100: -0.920

Variant links:

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]

SLC29A1 links:

POLR1C (HGNC:):

POLR1C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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 no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 401 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC29A1	NM_001372327.1 linkuse as main transcript	c.-52+8C>T		splice_region_variant, intron_variant		ENST00000371755.9	NP_001359256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC29A1	ENST00000371755.9 linkuse as main transcript	c.-52+8C>T		splice_region_variant, intron_variant		1	NM_001372327.1	ENSP00000360820	P1	Q99808-1

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

400

AN:

152010

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00218

AC XY:

AN XY:

41286

show subpopulations

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.:

Cov.:

AF XY:

0.00426

AC XY:

2186

AN XY:

513522

show subpopulations

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.:

Cov.:

AF XY:

0.00198

AC XY:

147

AN XY:

74376

show subpopulations

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.:

Bravo

AF:

0.00250

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC29A1-related disorder

Benign:1

Likely benign, no assertion criteria provided

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over