Genetic Variant ABCC3:p.Lys13Asn (chr17-50634975-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003786.4(ABCC3):c.39G>T(p.Lys13Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ABCC3
NM_003786.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.75

Publications

8 publications found

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:

ENSG00000251239 (HGNC:):

ENSG00000251239 links:

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ACMG classification

Classification was made for transcript

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=0.18642905).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003786.4. 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
	ABCC3	NM_003786.4	MANE Select	c.39G>T	p.Lys13Asn	missense	Exon 1 of 31	NP_003777.2
	ABCC3	NM_001144070.2		c.39G>T	p.Lys13Asn	missense	Exon 1 of 12	NP_001137542.1	O15438-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCC3	ENST00000285238.13	TSL:1 MANE Select	c.39G>T	p.Lys13Asn	missense	Exon 1 of 31	ENSP00000285238.8	O15438-1
ABCC3	ENST00000427699.5	TSL:1	c.39G>T	p.Lys13Asn	missense	Exon 1 of 12	ENSP00000395160.1	O15438-5
ABCC3	ENST00000871907.1		c.39G>T	p.Lys13Asn	missense	Exon 1 of 31	ENSP00000541966.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1108008

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

526206

African (AFR)

AF:

0.00

AC:

AN:

23708

American (AMR)

AF:

0.00

AC:

AN:

9396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14538

East Asian (EAS)

AF:

0.00

AC:

AN:

27540

South Asian (SAS)

AF:

0.00

AC:

AN:

23920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3008

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

932370

Other (OTH)

AF:

0.00

AC:

AN:

44422

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.094

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.020

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.64

M_CAP

Benign

0.016

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

PhyloP100

3.7

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.076

Sift

Benign

0.22

Sift4G

Benign

0.25

Polyphen

0.027

Vest4

0.24

MutPred

0.46

Loss of methylation at K13 (P = 0.0013)

MVP

0.51

MPC

0.21

ClinPred

0.93

GERP RS

3.9

PromoterAI

0.020

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over