rs41281802

Variant names:

• chr6-43444344-C-A
• rs41281802
• NM_001198934.2:c.2680C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-43444344-C-A
• chr6-43444344-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001198934.2(ABCC10):​c.2680C>A​(p.Leu894Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,192 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L894L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ABCC10 NM_001198934.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.33

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC10	NM_001198934.2	c.2680C>A	p.Leu894Ile	missense_variant	Exon 12 of 22	ENST00000372530.9	NP_001185863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC10	ENST00000372530.9	c.2680C>A	p.Leu894Ile	missense_variant	Exon 12 of 22	2	NM_001198934.2	ENSP00000361608.4
ABCC10	ENST00000244533.7	c.2596C>A	p.Leu866Ile	missense_variant	Exon 10 of 20	1		ENSP00000244533.3
ABCC10	ENST00000463024.1	n.2408C>A		non_coding_transcript_exon_variant	Exon 6 of 16	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454192 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723288

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33094

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 43256

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25562

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39648

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 85286

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53052

Gnomad4 NFE exome AF: 9.02e-7 AC: 1 AN: 1108756

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60034

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (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 v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.91	P;D
Vest4		0.49
MutPred		0.61		Gain of sheet (P = 0.0266);.;
MVP		0.72
MPC		0.71
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.59
gMVP		0.20
Mutation Taster		=80/20	polymorphism

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: rs41281802; hg19: chr6-43412082;