chr11-35432519-C-T
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001001991.3(PAMR1):c.2000G>A(p.Gly667Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,146 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
PAMR1
NM_001001991.3 missense
NM_001001991.3 missense
Scores
9
4
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.84
Genes affected
PAMR1 (HGNC:24554): (peptidase domain containing associated with muscle regeneration 1) Predicted to enable calcium ion binding activity and serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
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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, 0.985
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAMR1 | NM_001001991.3 | c.2000G>A | p.Gly667Asp | missense_variant | 11/11 | ENST00000619888.5 | |
PAMR1 | NM_015430.4 | c.2051G>A | p.Gly684Asp | missense_variant | 12/12 | ||
PAMR1 | NM_001282675.2 | c.1880G>A | p.Gly627Asp | missense_variant | 13/13 | ||
PAMR1 | NM_001282676.2 | c.1667G>A | p.Gly556Asp | missense_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAMR1 | ENST00000619888.5 | c.2000G>A | p.Gly667Asp | missense_variant | 11/11 | 1 | NM_001001991.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251180Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135728
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727246
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74390
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
D;D;.;.;.;.
Vest4
MutPred
0.85
.;Gain of phosphorylation at T665 (P = 0.1115);.;.;.;.;
MVP
ClinPred
D
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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