16-48088014-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001393797.1(ABCC12):c.3547G>A(p.Val1183Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCC12 NM_001393797.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

Genes affected

ABCC12 (HGNC:14640): (ATP binding cassette subfamily C member 12) This gene is a member of the superfamily of ATP-binding cassette (ABC) transporters and the encoded protein contains two ATP-binding domains and 12 transmembrane regions. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies: ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White. This gene is a member of the MRP subfamily which is involved in multi-drug resistance. This gene and another subfamily member are arranged head-to-tail on chromosome 16q12.1. Increased expression of this gene is associated with breast cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC12	NM_001393797.1	c.3547G>A	p.Val1183Met	missense_variant	27/31	ENST00000311303.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC12	ENST00000311303.8	c.3547G>A	p.Val1183Met	missense_variant	27/31	1	NM_001393797.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.3547G>A (p.V1183M) alteration is located in exon 25 (coding exon 25) of the ABCC12 gene. This alteration results from a G to A substitution at nucleotide position 3547, causing the valine (V) at amino acid position 1183 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Benign	17
Dann	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N
REVEL	Pathogenic	0.66
Sift	Benign	0.046	D
Sift4G	Benign	0.067	T
Polyphen		0.85	P
Vest4		0.44
MutPred		0.49		Loss of sheet (P = 0.1907);
MVP		0.72
MPC		0.34
ClinPred		0.93	D
GERP RS		4.1
Varity_R		0.15
gMVP		0.72

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: chr16-48121925;