rs2031089372

Variant names:

• chr13-95021640-G-A
• rs2031089372
• NM_005845.5:c.3913C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005845.5(ABCC4):​c.3913C>T​(p.His1305Tyr) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCC4 NM_005845.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• qualitative platelet defect

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

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=0.10181764).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005845.5. 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
	ABCC4	NM_005845.5	MANE Select	c.3913C>T	p.His1305Tyr	missense	Exon 31 of 31	NP_005836.2	O15439-1
	ABCC4	NM_001301829.2		c.3772C>T	p.His1258Tyr	missense	Exon 30 of 30	NP_001288758.1	O15439-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC4	ENST00000645237.2	MANE Select	c.3913C>T	p.His1305Tyr	missense	Exon 31 of 31	ENSP00000494609.1	O15439-1
	ABCC4	ENST00000967420.1		c.3937C>T	p.His1313Tyr	missense	Exon 31 of 31	ENSP00000637479.1
	ABCC4	ENST00000967421.1		c.3910C>T	p.His1304Tyr	missense	Exon 31 of 31	ENSP00000637480.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.067
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	4.4
DANN	Benign	0.50
DEOGEN2	Benign	0.078	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.83	L
PhyloP100		1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.20
Sift	Benign	0.060	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.081
MutPred		0.49		Gain of sheet (P = 4e-04)
MVP		0.59
MPC		0.27
ClinPred		0.080	T
GERP RS		1.9
Varity_R		0.026
gMVP		0.59
Mutation Taster		=98/2	polymorphism

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: rs2031089372; hg19: chr13-95673894;