NM_005845.5:c.3844G>T

Variant names:

• chr13-95034631-C-A
• NM_005845.5:c.3844G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005845.5(ABCC4):​c.3844G>T​(p.Ala1282Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ABCC4 NM_005845.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2590343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC4	NM_005845.5	c.3844G>T	p.Ala1282Ser	missense_variant	Exon 30 of 31	ENST00000645237.2	NP_005836.2
ABCC4	NM_001301829.2	c.3703G>T	p.Ala1235Ser	missense_variant	Exon 29 of 30		NP_001288758.1
ABCC4	XM_047430034.1	c.3715G>T	p.Ala1239Ser	missense_variant	Exon 30 of 31		XP_047285990.1
ABCC4	XM_047430035.1	c.3295G>T	p.Ala1099Ser	missense_variant	Exon 27 of 28		XP_047285991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC4	ENST00000645237.2	c.3844G>T	p.Ala1282Ser	missense_variant	Exon 30 of 31		NM_005845.5	ENSP00000494609.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461746 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727194

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T;T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	.;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Uncertain	0.15	D
MutationAssessor	Benign	1.8	L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.65	.;N;.
REVEL	Uncertain	0.34
Sift	Benign	0.24	.;T;.
Sift4G	Benign	0.47	.;T;.
Polyphen		0.67	P;P;B
Vest4		0.19
MutPred		0.36		Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);.;
MVP		0.81
MPC		0.42
ClinPred		0.71	D
GERP RS		5.3
Varity_R		0.063
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-95686885;