rs748411158

Variant names:

• chr6-44223649-C-A
• rs748411158
• NM_001372327.1:c.-52+8C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-44223649-C-A
• chr6-44223649-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001372327.1(SLC29A1):​c.-52+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000952 in 1,050,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: SLC29A1 NM_001372327.1 splice_region, intron
• Scores: Splicing: ADA: 0.00007013
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.920
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372327.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A1	NM_001372327.1	MANE Select	c.-52+8C>A		splice_region intron	N/A	NP_001359256.1	Q99808-1
	SLC29A1	NM_001078177.2		c.-468C>A		5_prime_UTR	Exon 1 of 14	NP_001071645.1	Q99808-1
	SLC29A1	NM_001304462.2		c.186+1964C>A		intron	N/A	NP_001291391.1	Q99808-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A1	ENST00000371755.9	TSL:1 MANE Select	c.-52+8C>A		splice_region intron	N/A	ENSP00000360820.3	Q99808-1
	SLC29A1	ENST00000393844.7	TSL:1	c.-51-3614C>A		intron	N/A	ENSP00000377427.1	Q99808-1
	SLC29A1	ENST00000371740.10	TSL:1	c.-159+8C>A		splice_region intron	N/A	ENSP00000360805.6	A0A2U3TZJ7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.52e-7 AC: 1 AN: 1050124 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 513522

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19614

American (AMR) AF: 0.00 AC: 0 AN: 17828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13686

East Asian (EAS) AF: 0.00 AC: 0 AN: 5030

South Asian (SAS) AF: 0.00 AC: 0 AN: 66118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2666

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 876642

Other (OTH) AF: 0.00 AC: 0 AN: 37276

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.8
DANN	Benign	0.89
PhyloP100		-0.92
PromoterAI		-0.12	Neutral
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)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs748411158; hg19: chr6-44191386;