rs2125740

chr6-43445197-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001198934.2(ABCC10):c.2913T>C(p.Tyr971=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,614,042 control chromosomes in the GnomAD database, including 1,464 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 0.056 (757 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (707 hom.)
• Consequence: ABCC10 NM_001198934.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

Genes affected

ABCC10 (HGNC:52): (ATP binding cassette subfamily C member 10) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This ABC full-transporter is a member of the MRP subfamily which is involved in multi-drug resistance. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.419 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC10	NM_001198934.2	c.2913T>C	p.Tyr971=	synonymous_variant	14/22	ENST00000372530.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC10	ENST00000372530.9	c.2913T>C	p.Tyr971=	synonymous_variant	14/22	2	NM_001198934.2	P2
ABCC10	ENST00000244533.7	c.2829T>C	p.Tyr943=	synonymous_variant	12/20	1		A2
ABCC10	ENST00000372512.2	n.98T>C		non_coding_transcript_exon_variant	1/2	3
ABCC10	ENST00000463024.1	n.2641T>C		non_coding_transcript_exon_variant	8/16	2

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8435 AN: 152072 Hom.: 756 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000824

Gnomad OTH AF: 0.0512

GnomAD3 exomes AF: 0.0145 AC: 3650 AN: 251458 Hom.: 281 AF XY: 0.0105 AC XY: 1421 AN XY: 135902

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.00957

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000598

Gnomad OTH exome AF: 0.00831

GnomAD4 exome AF: 0.00583 AC: 8528 AN: 1461852 Hom.: 707 Cov.: 35 AF XY: 0.00495 AC XY: 3599 AN XY: 727238

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000383

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000353

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.0556 AC: 8457 AN: 152190 Hom.: 757 Cov.: 32 AF XY: 0.0531 AC XY: 3951 AN XY: 74414

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0175

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000824

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.00976 Hom.: 248

Bravo AF: 0.0638

Asia WGS AF: 0.0100 AC: 36 AN: 3462

EpiCase AF: 0.000491

EpiControl AF: 0.000948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.29
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2125740; hg19: chr6-43412935;