NM_001393797.1:c.4027G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• 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 0 ACMG points.

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

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.4027G>C	p.Glu1343Gln	missense	Exon 31 of 31	NP_001380726.1
	ABCC12	NM_033226.3		c.4027G>C	p.Glu1343Gln	missense	Exon 31 of 31	NP_150229.2	Q96J65-1
	ABCC12	NM_001393799.1		c.649G>C	p.Glu217Gln	missense	Exon 7 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.4027G>C	p.Glu1343Gln	missense	Exon 31 of 31	ENSP00000311030.4
	ABCC12	ENST00000497206.6	TSL:1	n.*939G>C		non_coding_transcript_exon	Exon 28 of 28	ENSP00000431232.1	Q96J65-2
	ABCC12	ENST00000529084.5	TSL:1	n.*1994G>C		non_coding_transcript_exon	Exon 29 of 29	ENSP00000434510.1	Q96J65-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.091
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
PhyloP100		1.1
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

Other links and lift over

dbSNP: rs1179474697; hg19: chr16-48117679;