rs8192690

Variant names:

• chr11-17393023-C-A
• NM_000352.6:c.4714G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-17393023-C-A
• chr11-17393023-C-G
• chr11-17393023-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_000352.6(ABCC8):​c.4714G>T​(p.Val1572Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ABCC8 NM_000352.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486

Genes affected

ABCC8 (HGNC:59): (ATP binding cassette subfamily C member 8) 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, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a modulator of ATP-sensitive potassium channels and insulin release. Mutations in the ABCC8 gene and deficiencies in the encoded protein have been observed in patients with hyperinsulinemic hypoglycemia of infancy, an autosomal recessive disorder of unregulated and high insulin secretion. Mutations have also been associated with non-insulin-dependent diabetes mellitus type II, an autosomal dominant disease of defective insulin secretion. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a domain ABC transporter 2 (size 234) in uniprot entity ABCC8_HUMAN there are 33 pathogenic changes around while only 3 benign (92%) in NM_000352.6
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3333171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC8	NM_000352.6	c.4714G>T	p.Val1572Phe	missense_variant	Exon 39 of 39	ENST00000389817.8	NP_000343.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC8	ENST00000389817.8	c.4714G>T	p.Val1572Phe	missense_variant	Exon 39 of 39	1	NM_000352.6	ENSP00000374467.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	.;.;D;.;.;.;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.95	D;.;D;D;D;D;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.33	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	0.50	.;.;N;.;.;.;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.8	.;.;D;D;.;.;.;.
REVEL	Uncertain	0.58
Sift	Uncertain	0.0060	.;.;D;D;.;.;.;.
Sift4G	Uncertain	0.059	.;.;T;T;.;.;.;.
Polyphen		0.86	.;.;P;.;.;.;.;.
Vest4		0.72, 0.72
MutPred		0.28		.;.;Loss of MoRF binding (P = 0.1399);.;.;.;Loss of MoRF binding (P = 0.1399);.;
MVP		0.86
MPC		1.1
ClinPred		0.89	D
GERP RS		1.3
Varity_R		0.31
gMVP		0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-17414570;