chr16-48175312-C-A

Variant names:

• chr16-48175312-C-A
• NM_001370497.1:c.3644G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001370497.1(ABCC11):​c.3644G>T​(p.Arg1215Leu) 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 pathogenic 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.989

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC11	NM_001370497.1	c.3644G>T	p.Arg1215Leu	missense_variant	Exon 26 of 30	ENST00000356608.7	NP_001357426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC11	ENST00000356608.7	c.3644G>T	p.Arg1215Leu	missense_variant	Exon 26 of 30	1	NM_001370497.1	ENSP00000349017.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	.;D;D;D
Eigen	Benign	0.14
Eigen_PC	Benign	0.048
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.88	D;.;.;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.99	D;D;D;D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Pathogenic	3.2	M;M;M;M
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.7	D;D;D;D
REVEL	Pathogenic	0.80
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.18	B;D;D;D
Vest4		0.96
MutPred		0.95		Gain of ubiquitination at K1217 (P = 0.1128);Gain of ubiquitination at K1217 (P = 0.1128);Gain of ubiquitination at K1217 (P = 0.1128);Gain of ubiquitination at K1217 (P = 0.1128);
MVP		0.92
MPC		0.51
ClinPred		0.99	D
GERP RS		1.9
Varity_R		0.85
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: chr16-48209223; COSMIC: COSV100750701;