chr6-43433136-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001198934.2(ABCC10):ā€‹c.1156A>Cā€‹(p.Thr386Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

ABCC10
NM_001198934.2 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCC10NM_001198934.2 linkuse as main transcriptc.1156A>C p.Thr386Pro missense_variant 3/22 ENST00000372530.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCC10ENST00000372530.9 linkuse as main transcriptc.1156A>C p.Thr386Pro missense_variant 3/222 NM_001198934.2 P2Q5T3U5-1
ABCC10ENST00000244533.7 linkuse as main transcriptc.1027A>C p.Thr343Pro missense_variant 1/201 A2Q5T3U5-2
ABCC10ENST00000372515.8 linkuse as main transcriptc.-78-99A>C intron_variant 5
ABCC10ENST00000443426.2 linkuse as main transcriptn.113-99A>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
83
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 GeneticsApr 27, 2022The c.1156A>C (p.T386P) alteration is located in exon 3 (coding exon 2) of the ABCC10 gene. This alteration results from a A to C substitution at nucleotide position 1156, causing the threonine (T) at amino acid position 386 to be replaced by a proline (P). 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
0.29
BayesDel_addAF
Pathogenic
0.50
D
BayesDel_noAF
Pathogenic
0.48
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.72
D;.
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.67
T;T
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Pathogenic
0.89
D
MutationAssessor
Pathogenic
3.4
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-5.2
D;D
REVEL
Pathogenic
0.92
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
D;D
Vest4
0.71
MutPred
0.67
Gain of disorder (P = 0.0839);.;
MVP
0.98
MPC
0.78
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.94
gMVP
0.83

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: rs1323291348; hg19: chr6-43400874; API