6-44221578-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000393844.7(SLC29A1):c.-52+1796T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC29A1 ENST00000393844.7 intron
• Scores: Splicing: ADA: 0.0002345
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.196

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 6-44221578-T-A is Benign according to our data. Variant chr6-44221578-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3044005.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC29A1	NM_001304462.2	c.87-8T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SLC29A1	NM_001304465.2	c.24+1796T>A		intron_variant
SLC29A1	NM_001304466.2	c.24+1796T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC29A1	ENST00000393844.7	c.-52+1796T>A		intron_variant		1		P1
SLC29A1	ENST00000371713.6	c.-151-8T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		P1
SLC29A1	ENST00000643028.2	c.-29+1796T>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8 AN: 148100 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000490

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000449

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00123 AC: 890 AN: 722554 Hom.: 0 Cov.: 15 AF XY: 0.00116 AC XY: 427 AN XY: 367156

Gnomad4 AFR exome AF: 0.000604

Gnomad4 AMR exome AF: 0.0000359

Gnomad4 ASJ exome AF: 0.000377

Gnomad4 EAS exome AF: 0.000271

Gnomad4 SAS exome AF: 0.000176

Gnomad4 FIN exome AF: 0.0000773

Gnomad4 NFE exome AF: 0.00153

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000540 AC: 8 AN: 148232 Hom.: 0 Cov.: 32 AF XY: 0.0000553 AC XY: 4 AN XY: 72382

Gnomad4 AFR AF: 0.0000489

Gnomad4 AMR AF: 0.000134

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000228

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000449

Gnomad4 OTH AF: 0.00

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

Jun 01, 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	-0.75
Cadd	Benign	5.4
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.0
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-44189315;