NM_005845.5:c.3310T>A

Variant names:

• chr13-95062760-A-T
• NM_005845.5:c.3310T>A

Variant summary

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

The NM_005845.5(ABCC4):​c.3310T>A​(p.Leu1104Met) 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.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ABCC4 NM_005845.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03

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]

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 rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3310T>A	p.Leu1104Met	missense_variant	Exon 26 of 31	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3169T>A	p.Leu1057Met	missense_variant	Exon 25 of 30		NP_001288758.1
ABCC4	XM_047430034.1	c.3181T>A	p.Leu1061Met	missense_variant	Exon 26 of 31		XP_047285990.1
ABCC4	XM_047430035.1	c.2761T>A	p.Leu921Met	missense_variant	Exon 23 of 28		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3310T>A	p.Leu1104Met	missense_variant	Exon 26 of 31		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.72	.;T;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.18	.;N;.
REVEL	Uncertain	0.40
Sift	Benign	0.12	.;T;.
Sift4G	Benign	0.098	.;T;.
Polyphen		0.59	P;P;B
Vest4		0.33
MutPred		0.66		Loss of catalytic residue at L1104 (P = 0.0308);Loss of catalytic residue at L1104 (P = 0.0308);.;
MVP		0.85
MPC		0.36
ClinPred		0.68	D
GERP RS		6.2
Varity_R		0.47
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr13-95715014;