rs63749823
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_001171.6(ABCC6):c.3961G>A(p.Gly1321Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,110 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 Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Consequence
ABCC6
NM_001171.6 missense
NM_001171.6 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 6.15
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 10 ACMG points.
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 5 uncertain in NM_001171.6
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.991
PP5
?
Variant 16-16154953-C-T is Pathogenic according to our data. Variant chr16-16154953-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 6580.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-16154953-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.3961G>A | p.Gly1321Ser | missense_variant | 28/31 | ENST00000205557.12 | |
ABCC6 | NM_001351800.1 | c.3619G>A | p.Gly1207Ser | missense_variant | 28/31 | ||
ABCC6 | NR_147784.1 | n.3623G>A | non_coding_transcript_exon_variant | 26/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.3961G>A | p.Gly1321Ser | missense_variant | 28/31 | 1 | NM_001171.6 | P1 | |
ABCC6 | ENST00000576204.6 | n.824G>A | non_coding_transcript_exon_variant | 1/2 | 5 | ||||
ABCC6 | ENST00000456970.6 | c.*970G>A | 3_prime_UTR_variant, NMD_transcript_variant | 26/29 | 2 | ||||
ABCC6 | ENST00000622290.5 | c.*133G>A | 3_prime_UTR_variant, NMD_transcript_variant | 29/32 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 31
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GnomAD4 exome Cov.: 32
GnomAD4 exome
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32
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74312
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2002 | - - |
Likely pathogenic, criteria provided, single submitter | research | PXE International | Mar 01, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Pathogenic
Sift
Uncertain
D;.
Sift4G
Pathogenic
D;.
Polyphen
D;.
Vest4
MutPred
Gain of glycosylation at G1321 (P = 0.0804);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at