rs778544828
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001171.6(ABCC6):c.118C>T(p.Pro40Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,504 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 (no stars).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ABCC6
NM_001171.6 missense
NM_001171.6 missense
Scores
9
5
5
Clinical Significance
Conservation
PhyloP100: 6.45
Genes affected
ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) 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). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.972
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.118C>T | p.Pro40Ser | missense_variant | 2/31 | ENST00000205557.12 | |
ABCC6 | NM_001079528.4 | c.118C>T | p.Pro40Ser | missense_variant | 2/2 | ||
ABCC6 | NM_001351800.1 | c.-256C>T | 5_prime_UTR_variant | 2/31 | |||
ABCC6 | NR_147784.1 | n.155C>T | non_coding_transcript_exon_variant | 2/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.118C>T | p.Pro40Ser | missense_variant | 2/31 | 1 | NM_001171.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD3 genomes
Cov.:
30
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461504Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727048
GnomAD4 exome
AF:
AC:
2
AN:
1461504
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
727048
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 30
GnomAD4 genome
Cov.:
30
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Uncertain:1
Uncertain significance, no assertion criteria provided | research | PXE International | Feb 16, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;.;.
REVEL
Pathogenic
Sift
Uncertain
D;.;.
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of catalytic residue at P40 (P = 0.1947);Loss of catalytic residue at P40 (P = 0.1947);Loss of catalytic residue at P40 (P = 0.1947);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at