chr17-50658104-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003786.4(ABCC3):​c.509G>A​(p.Arg170His) variant causes a missense change. The variant allele was found at a frequency of 0.000108 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ABCC3
NM_003786.4 missense

Scores

3
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.48
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3226778).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCC3NM_003786.4 linkuse as main transcriptc.509G>A p.Arg170His missense_variant 5/31 ENST00000285238.13
ABCC3NM_001144070.2 linkuse as main transcriptc.509G>A p.Arg170His missense_variant 5/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCC3ENST00000285238.13 linkuse as main transcriptc.509G>A p.Arg170His missense_variant 5/311 NM_003786.4 P1O15438-1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152140
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000636
AC:
16
AN:
251470
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000112
AC:
164
AN:
1461856
Hom.:
0
Cov.:
32
AF XY:
0.000111
AC XY:
81
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000133
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152140
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000560
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000218
EpiControl
AF:
0.000356

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 12, 2023The c.509G>A (p.R170H) alteration is located in exon 5 (coding exon 5) of the ABCC3 gene. This alteration results from a G to A substitution at nucleotide position 509, causing the arginine (R) at amino acid position 170 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.25
.;T
Eigen
Benign
0.088
Eigen_PC
Benign
0.19
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.32
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.8
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.47
T
PROVEAN
Pathogenic
-4.5
D;D
REVEL
Benign
0.16
Sift
Benign
0.036
D;T
Sift4G
Benign
0.063
T;T
Polyphen
0.51
P;B
Vest4
0.58
MutPred
0.56
Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP
0.60
MPC
0.22
ClinPred
0.76
D
GERP RS
4.7
Varity_R
0.18
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs200670648; hg19: chr17-48735465; API