13-95053126-G-C

Position:

• chr13-95053126-G-C

Variant summary

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

The NM_005845.5(ABCC4):​c.3425C>G​(p.Thr1142Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1142M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCC4 NM_005845.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.44

Genes affected

ABCC4 (HGNC:55): (ATP binding cassette subfamily C member 4 (PEL blood group)) 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 protein is a member of the MRP subfamily which is involved in multi-drug resistance. This family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ABCC4 (HGNC:):

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	Protein	UniProt
ABCC4	NM_005845.5	c.3425C>G	p.Thr1142Arg	missense_variant	27/31	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3284C>G	p.Thr1095Arg	missense_variant	26/30		NP_001288758.1
ABCC4	XM_047430034.1	c.3296C>G	p.Thr1099Arg	missense_variant	27/31		XP_047285990.1
ABCC4	XM_047430035.1	c.2876C>G	p.Thr959Arg	missense_variant	24/28		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3425C>G	p.Thr1142Arg	missense_variant	27/31		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;D;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.2	M;M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.0	.;D;.
REVEL	Uncertain	0.59
Sift	Benign	0.091	.;T;.
Sift4G	Benign	0.19	.;T;.
Polyphen		0.77	P;P;B
Vest4		0.47
MutPred		0.58		Loss of phosphorylation at T1142 (P = 0.0502);Loss of phosphorylation at T1142 (P = 0.0502);.;
MVP		0.92
MPC		0.77
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.36
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs11568644; hg19: chr13-95705380; COSMIC: COSV65315054;