rs2277122

chr6-43438763-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001198934.2(ABCC10):c.2095C>T(p.Leu699=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 1,614,142 control chromosomes in the GnomAD database, including 2,701 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 0.041 (213 hom., cov: 33)
  • Exomes 𝑓: 0.051 (2488 hom.)
• Consequence: ABCC10 NM_001198934.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP7: Synonymous conserved (PhyloP=-0.104 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC10	NM_001198934.2	c.2095C>T	p.Leu699=	synonymous_variant	8/22	ENST00000372530.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC10	ENST00000372530.9	c.2095C>T	p.Leu699=	synonymous_variant	8/22	2	NM_001198934.2	P2

Frequencies

GnomAD3 genomes AF: 0.0411 AC: 6248 AN: 152166 Hom.: 214 Cov.: 33

Gnomad AFR AF: 0.00924

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0402

GnomAD3 exomes AF: 0.0649 AC: 16326 AN: 251418 Hom.: 785 AF XY: 0.0666 AC XY: 9043 AN XY: 135878

Gnomad AFR exome AF: 0.00695

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.0503

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.136

Gnomad FIN exome AF: 0.0316

Gnomad NFE exome AF: 0.0444

Gnomad OTH exome AF: 0.0598

GnomAD4 exome AF: 0.0507 AC: 74057 AN: 1461858 Hom.: 2488 Cov.: 31 AF XY: 0.0527 AC XY: 38293 AN XY: 727244

Gnomad4 AFR exome AF: 0.00699

Gnomad4 AMR exome AF: 0.0970

Gnomad4 ASJ exome AF: 0.0504

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.0329

Gnomad4 NFE exome AF: 0.0426

Gnomad4 OTH exome AF: 0.0529

GnomAD4 genome AF: 0.0410 AC: 6247 AN: 152284 Hom.: 213 Cov.: 33 AF XY: 0.0433 AC XY: 3228 AN XY: 74466

Gnomad4 AFR AF: 0.00921

Gnomad4 AMR AF: 0.0684

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.0426

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0465 Hom.: 443

Bravo AF: 0.0410

Asia WGS AF: 0.119 AC: 413 AN: 3478

EpiCase AF: 0.0480

EpiControl AF: 0.0484

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	9.4
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs2277122; hg19: chr6-43406501;