rs78678589
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_001171.6(ABCC6):c.951C>G(p.Ser317Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S317?) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 32)
Consequence
ABCC6
NM_001171.6 missense
NM_001171.6 missense
Scores
5
4
10
Clinical Significance
Conservation
PhyloP100: 2.73
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 Pathogenic. Variant got 11 ACMG points.
PM1
In a domain ABC transmembrane type-1 1 (size 282) in uniprot entity MRP6_HUMAN there are 31 pathogenic changes around while only 9 benign (78%) in NM_001171.6
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr16-16203457-G-Y is described in Lovd as [Pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.975
PP5
Variant 16-16203457-G-C is Pathogenic according to our data. Variant chr16-16203457-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 433374.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ABCC6 | NM_001171.6 | c.951C>G | p.Ser317Arg | missense_variant | Exon 8 of 31 | ENST00000205557.12 | NP_001162.5 | |
| ABCC6 | NM_001351800.1 | c.609C>G | p.Ser203Arg | missense_variant | Exon 8 of 31 | NP_001338729.1 | ||
| ABCC6 | NR_147784.1 | n.988C>G | non_coding_transcript_exon_variant | Exon 8 of 29 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Pathogenic:1
Mar 01, 2021
PXE International
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: research
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Pathogenic
Sift
Benign
T;.
Sift4G
Benign
T;D
Polyphen
P;.
Vest4
MutPred
Gain of methylation at S317 (P = 0.0168);Gain of methylation at S317 (P = 0.0168);
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