16-48083768-C-G

Variant names:

• chr16-48083768-C-G
• rs1179474697
• NM_001393797.1:c.4027G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393797.1(ABCC12):​c.4027G>C​(p.Glu1343Gln) 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. 15/21 in silico tools predict a benign outcome for this variant. 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: 1.11

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09060171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC12	NM_001393797.1	c.4027G>C	p.Glu1343Gln	missense_variant	Exon 31 of 31	ENST00000311303.8	NP_001380726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC12	ENST00000311303.8	c.4027G>C	p.Glu1343Gln	missense_variant	Exon 31 of 31	1	NM_001393797.1	ENSP00000311030.4

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

Jan 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4027G>C (p.E1343Q) alteration is located in exon 29 (coding exon 29) of the ABCC12 gene. This alteration results from a G to C substitution at nucleotide position 4027, causing the glutamic acid (E) at amino acid position 1343 to be replaced by a glutamine (Q). 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	0.091
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.54
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.030	N
REVEL	Uncertain	0.32
Sift	Benign	0.60	T
Sift4G	Benign	0.64	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.29		Loss of stability (P = 0.0812);
MVP		0.80
MPC		0.14
ClinPred		0.19	T
GERP RS		4.5
Varity_R		0.14
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs1179474697; hg19: chr16-48117679;