rs28940268
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_173076.3(ABCA12):c.4142G>A(p.Gly1381Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
ABCA12
NM_173076.3 missense
NM_173076.3 missense
Scores
17
1
1
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
ABCA12 (HGNC:14637): (ATP binding cassette subfamily A member 12) The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PM1
In a domain ABC transporter 1 (size 231) in uniprot entity ABCAC_HUMAN there are 9 pathogenic changes around while only 2 benign (82%) in NM_173076.3
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.994
PP5
Variant 2-214986563-C-T is Pathogenic according to our data. Variant chr2-214986563-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2854.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-214986563-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCA12 | NM_173076.3 | c.4142G>A | p.Gly1381Glu | missense_variant | 28/53 | ENST00000272895.12 | NP_775099.2 | |
ABCA12 | NM_015657.4 | c.3188G>A | p.Gly1063Glu | missense_variant | 20/45 | NP_056472.2 | ||
ABCA12 | XM_011510951.3 | c.4151G>A | p.Gly1384Glu | missense_variant | 28/53 | XP_011509253.1 | ||
ABCA12 | NR_103740.2 | n.4640G>A | non_coding_transcript_exon_variant | 30/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCA12 | ENST00000272895.12 | c.4142G>A | p.Gly1381Glu | missense_variant | 28/53 | 1 | NM_173076.3 | ENSP00000272895.7 | ||
ABCA12 | ENST00000389661.4 | c.3188G>A | p.Gly1063Glu | missense_variant | 20/45 | 1 | ENSP00000374312.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive congenital ichthyosis 4A Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 15, 2003 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of sheet (P = 0.0827);.;
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