chr6-43432372-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001198934.2(ABCC10):​c.392G>A​(p.Arg131Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,628 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: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ABCC10
NM_001198934.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.58
Variant links:
Genes affected
ABCC10 (HGNC:52): (ATP binding cassette subfamily C member 10) 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, and White). This ABC full-transporter is a member of the MRP subfamily which is involved in multi-drug resistance. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21858147).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCC10NM_001198934.2 linkuse as main transcriptc.392G>A p.Arg131Gln missense_variant 3/22 ENST00000372530.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCC10ENST00000372530.9 linkuse as main transcriptc.392G>A p.Arg131Gln missense_variant 3/222 NM_001198934.2 P2Q5T3U5-1
ABCC10ENST00000244533.7 linkuse as main transcriptc.263G>A p.Arg88Gln missense_variant 1/201 A2Q5T3U5-2
ABCC10ENST00000372515.8 linkuse as main transcriptc.-78-863G>A intron_variant 5
ABCC10ENST00000443426.2 linkuse as main transcriptn.113-863G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250380
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135458
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460628
Hom.:
0
Cov.:
87
AF XY:
0.00000550
AC XY:
4
AN XY:
726708
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 GeneticsJul 09, 2021The c.392G>A (p.R131Q) alteration is located in exon 3 (coding exon 2) of the ABCC10 gene. This alteration results from a G to A substitution at nucleotide position 392, causing the arginine (R) at amino acid position 131 to be replaced by a glutamine (Q). 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
0.094
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;.
Eigen
Benign
0.025
Eigen_PC
Benign
0.17
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-2.5
D;D
REVEL
Benign
0.11
Sift
Uncertain
0.029
D;D
Sift4G
Uncertain
0.049
D;T
Polyphen
0.18
B;B
Vest4
0.42
MutPred
0.36
Loss of methylation at R131 (P = 0.0121);.;
MVP
0.57
MPC
0.20
ClinPred
0.93
D
GERP RS
4.9
Varity_R
0.21
gMVP
0.72

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.

Other links and lift over

dbSNP: rs1327817713; hg19: chr6-43400110; COSMIC: COSV99768148; COSMIC: COSV99768148; API