rs1678339

chr13-95075526-T-Achr13-95075526-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005845.5(ABCC4):c.2712A>T(p.Leu904Phe) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABCC4 NM_005845.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC4	NM_005845.5	c.2712A>T	p.Leu904Phe	missense_variant	22/31	ENST00000645237.2
ABCC4	NM_001301829.2	c.2571A>T	p.Leu857Phe	missense_variant	21/30
ABCC4	XM_047430034.1	c.2583A>T	p.Leu861Phe	missense_variant	22/31
ABCC4	XM_047430035.1	c.2163A>T	p.Leu721Phe	missense_variant	19/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC4	ENST00000645237.2	c.2712A>T	p.Leu904Phe	missense_variant	22/31		NM_005845.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
Cadd	Benign	13
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.10	N
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Benign	0.99	L;L;.
MutationTaster	Benign	0.00023	P;P
PrimateAI	Uncertain	0.75	T
Polyphen		0.86	P;P;P
Vest4		0.58
MutPred		0.70		Loss of disorder (P = 0.1686);Loss of disorder (P = 0.1686);.;
MVP		0.51
MPC		0.83
ClinPred		0.98	D
GERP RS		-4.7
Varity_R		0.45
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1678339; hg19: chr13-95727780;