dbSNP rs2277624: ABCC3:p.His1314Gln (chr17-50683744-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003786.4(ABCC3):c.3942C>G(p.His1314Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict 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 Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ABCC3
NM_003786.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.25

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032970607).

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.3942C>G	p.His1314Gln	missense	Exon 27 of 31	NP_003777.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCC3	ENST00000285238.13	TSL:1 MANE Select	c.3942C>G	p.His1314Gln	missense	Exon 27 of 31	ENSP00000285238.8	O15438-1
ABCC3	ENST00000503337.1	TSL:1	n.1136C>G		non_coding_transcript_exon	Exon 2 of 6
ABCC3	ENST00000871907.1		c.4047C>G	p.His1349Gln	missense	Exon 27 of 31	ENSP00000541966.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452616

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722628

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32726

American (AMR)

AF:

0.00

AC:

AN:

42144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25738

East Asian (EAS)

AF:

0.00

AC:

AN:

39192

South Asian (SAS)

AF:

0.00

AC:

AN:

85324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108654

Other (OTH)

AF:

0.00

AC:

AN:

59988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.0050

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.17

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.65

M_CAP

Benign

0.025

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.56

MutationAssessor

Benign

-0.54

PhyloP100

-4.2

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.010

REVEL

Benign

0.24

Sift

Benign

0.78

Sift4G

Benign

0.68

Polyphen

0.014

Vest4

0.10

MutPred

0.32

Gain of sheet (P = 0.0827)

MVP

0.60

MPC

0.16

ClinPred

0.048

GERP RS

-12

Varity_R

0.064

gMVP

0.25

Mutation Taster

=90/10

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over