NM_003786.4:c.39G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2647939.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

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>C	p.Lys13Asn	missense	Exon 1 of 31	NP_003777.2
	ABCC3	NM_001144070.2		c.39G>C	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>C	p.Lys13Asn	missense	Exon 1 of 31	ENSP00000285238.8	O15438-1
ABCC3	ENST00000427699.5	TSL:1	c.39G>C	p.Lys13Asn	missense	Exon 1 of 12	ENSP00000395160.1	O15438-5
ABCC3	ENST00000871907.1		c.39G>C	p.Lys13Asn	missense	Exon 1 of 31	ENSP00000541966.1

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

GnomAD2 exomes

AF:

0.00561

AC:

112

AN:

19972

AF XY:

0.00627

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 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

African (AFR)

AF:

0.00186

AC:

AN:

23708

American (AMR)

AF:

0.00426

AC:

AN:

9396

Ashkenazi Jewish (ASJ)

AF:

0.0120

AC:

175

AN:

14538

East Asian (EAS)

AF:

0.0000363

AC:

AN:

27540

South Asian (SAS)

AF:

0.000920

AC:

AN:

23920

European-Finnish (FIN)

AF:

0.0101

AC:

294

AN:

29104

Middle Eastern (MID)

AF:

0.00798

AC:

AN:

3008

European-Non Finnish (NFE)

AF:

0.00782

AC:

7291

AN:

932360

Other (OTH)

AF:

0.00702

AC:

312

AN:

44420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

451

903

1354

1806

2257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00628

AC:

957

AN:

152286

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

442

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41574

American (AMR)

AF:

0.00464

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00145

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00764

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0100

AC:

681

AN:

68010

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

102

153

204

255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.51

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

0.64

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

3.7

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.075

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

0.051

GERP RS

3.9

PromoterAI

0.090

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.5

Varity_R

0.23

gMVP

0.13

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over