NM_001393797.1:c.3547G>A

Variant names:

• chr16-48088014-C-T
• NM_001393797.1:c.3547G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393797.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC12	NM_001393797.1	MANE Select	c.3547G>A	p.Val1183Met	missense	Exon 27 of 31	NP_001380726.1
	ABCC12	NM_033226.3		c.3547G>A	p.Val1183Met	missense	Exon 27 of 31	NP_150229.2	Q96J65-1
	ABCC12	NM_001393799.1		c.169G>A	p.Val57Met	missense	Exon 3 of 7	NP_001380728.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC12	ENST00000311303.8	TSL:1 MANE Select	c.3547G>A	p.Val1183Met	missense	Exon 27 of 31	ENSP00000311030.4
	ABCC12	ENST00000497206.6	TSL:1	n.*538G>A		non_coding_transcript_exon	Exon 25 of 28	ENSP00000431232.1	Q96J65-2
	ABCC12	ENST00000526251.1	TSL:1	n.381G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.3
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

Other links and lift over

hg19: chr16-48121925;