rs35605

Positions:

• chr16-16068162-T-A
• chr16-16068162-T-C

Variant summary

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

The NM_004996.4(ABCC1):​c.1684T>A​(p.Leu562Met) 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: ABCC1 NM_004996.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480

Genes affected

ABCC1 (HGNC:51): (ATP binding cassette subfamily C member 1 (ABCC1 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 full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutatione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternatively spliced variants of this gene have been described but their full-length nature is unknown. [provided by RefSeq, Apr 2012]

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, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.1684T>A	p.Leu562Met	missense_variant	13/31	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.1684T>A	p.Leu562Met	missense_variant	13/31	1	NM_004996.4	ENSP00000382342	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Uncertain	0.65	D
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	0.036	P;P;P;P;P;P
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;.
Vest4		0.52
MutPred		0.57		Loss of catalytic residue at L562 (P = 0.0962);.;
MVP		0.80
MPC		1.1
ClinPred		0.85	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs35605; hg19: chr16-16162019;