Variant 17-50634975-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003786.4(ABCC3):c.39G>C(p.Lys13Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00727 in 1,260,280 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 34)

Exomes 𝑓: 0.0074 ( 30 hom. )

Consequence

ABCC3
NM_003786.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.75

Variant links:

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]

ABCC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056319833).

BP6

Variant 17-50634975-G-C is Benign according to our data. Variant chr17-50634975-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2647939.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC3	NM_003786.4 linkuse as main transcript	c.39G>C	p.Lys13Asn	missense_variant	1/31	ENST00000285238.13
ABCC3	NM_001144070.2 linkuse as main transcript	c.39G>C	p.Lys13Asn	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC3	ENST00000285238.13 linkuse as main transcript	c.39G>C	p.Lys13Asn	missense_variant	1/31	1	NM_003786.4	P1	O15438-1

Frequencies

GnomAD3 genomes

AF:

0.00630

AC:

959

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00764

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00561

AC:

112

AN:

19972

Hom.:

AF XY:

0.00627

AC XY:

AN XY:

11320

show subpopulations

Gnomad AFR exome

AF:

0.00230

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00453

Gnomad NFE exome

AF:

0.00846

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00740

AC:

8203

AN:

1107994

Hom.:

Cov.:

AF XY:

0.00746

AC XY:

3925

AN XY:

526198

show subpopulations

Gnomad4 AFR exome

AF:

0.00186

Gnomad4 AMR exome

AF:

0.00426

Gnomad4 ASJ exome

AF:

0.0120

Gnomad4 EAS exome

AF:

0.0000363

Gnomad4 SAS exome

AF:

0.000920

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.00782

Gnomad4 OTH exome

AF:

0.00702

GnomAD4 genome

AF:

0.00628

AC:

957

AN:

152286

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

442

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00764

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00460

Hom.:

Bravo

AF:

0.00561

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00111

AC:

ESP6500EA

AF:

0.00566

AC:

ExAC

AF:

0.00326

AC:

318

Asia WGS

AF:

0.00116

AC:

AN:

3454

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

ABCC3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.094

.;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.020

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.64

.;T;T

MetaRNN

Benign

0.0056

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;L;L

MutationTaster

Benign

0.90

D;D;N

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.0

D;N;N

REVEL

Benign

0.075

Sift

Benign

0.22

.;T;T

Sift4G

Benign

0.25

.;T;T

Polyphen

0.027, 0.089

.;B;B

Vest4

0.24

MutPred

0.46

Loss of methylation at K13 (P = 0.0013);Loss of methylation at K13 (P = 0.0013);Loss of methylation at K13 (P = 0.0013);

MVP

0.51

MPC

0.21

ClinPred

0.051

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.5

Varity_R

0.23

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over