NM_003786.4:c.182G>T

Variant names:

• chr17-50655968-G-T
• rs760576754
• NM_003786.4:c.182G>T

Variant summary

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

The NM_003786.4(ABCC3):​c.182G>T​(p.Arg61Leu) 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 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ABCC3 NM_003786.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

Genes affected

ABCC3 (HGNC:54): (ATP binding cassette subfamily C member 3) 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. The specific function of this protein has not yet been determined; however, this protein may play a role in the transport of biliary and intestinal excretion of organic anions. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

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=0.155772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC3	NM_003786.4	c.182G>T	p.Arg61Leu	missense_variant	Exon 2 of 31	ENST00000285238.13	NP_003777.2
ABCC3	NM_001144070.2	c.182G>T	p.Arg61Leu	missense_variant	Exon 2 of 12		NP_001137542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC3	ENST00000285238.13	c.182G>T	p.Arg61Leu	missense_variant	Exon 2 of 31	1	NM_003786.4	ENSP00000285238.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251432 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135898

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727242

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.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.3
DANN	Benign	0.97
DEOGEN2	Benign	0.28	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.19	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Benign	0.11
Sift	Benign	0.25	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.040	B;B
Vest4		0.32
MutPred		0.67		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.27
MPC		0.20
ClinPred		0.95	D
GERP RS		-7.5
Varity_R		0.059
gMVP		0.18

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: rs760576754; hg19: chr17-48733329;