Genetic Variant NM_001370497.1:c.3746A>G (chr16-48170920-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001370497.1(ABCC11):c.3746A>G(p.Asp1249Gly) 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. 13/21 in silico tools predict 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: 32)

Consequence

ABCC11
NM_001370497.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.757

Variant links:

Genes affected

ABCC11 (HGNC:14639): (ATP binding cassette subfamily C member 11) 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 ABC full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a SNP in this gene is responsible for determination of human earwax type. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

ABCC11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26649293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC11	NM_001370497.1 link	c.3746A>G	p.Asp1249Gly	missense_variant	Exon 27 of 30	ENST00000356608.7	NP_001357426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC11	ENST00000356608.7 link	c.3746A>G	p.Asp1249Gly	missense_variant	Exon 27 of 30	1	NM_001370497.1	ENSP00000349017.2		Q96J66-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.47

.;T;T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.82

T;.;.;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

1.3

L;L;L;L

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Benign

0.21

Sift

Benign

0.078

T;T;T;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.62

P;B;B;B

Vest4

0.30

MutPred

0.47

Gain of MoRF binding (P = 0.1112);Gain of MoRF binding (P = 0.1112);Gain of MoRF binding (P = 0.1112);Gain of MoRF binding (P = 0.1112);

MVP

0.85

MPC

0.13

ClinPred

0.23

GERP RS

2.4

Varity_R

0.24

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over