1-109231677-G-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PS1_ModeratePM2PP2PP5
The NM_006513.4(SARS1):c.638G>T(p.Arg213Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classifications from unflagged records (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.
Frequency
Genomes: not found (cov: 32)
Consequence
SARS1
NM_006513.4 missense
NM_006513.4 missense
Scores
2
12
5
Clinical Significance
Conservation
PhyloP100: 5.65
Genes affected
SARS1 (HGNC:10537): (seryl-tRNA synthetase 1) This gene belongs to the class II amino-acyl tRNA family. The encoded enzyme catalyzes the transfer of L-serine to tRNA (Ser) and is related to bacterial and yeast counterparts. Multiple alternatively spliced transcript variants have been described but the biological validity of all variants is unknown. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PS1
Transcript NM_006513.4 (SARS1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SARS1. . Gene score misZ 2.6571 (greater than the threshold 3.09). Trascript score misZ 3.2534 (greater than threshold 3.09). GenCC has associacion of gene with autosomal recessive non-syndromic intellectual disability, neurodevelopmental disorder with microcephaly, ataxia, and seizures.
PP5
Variant 1-109231677-G-T is Pathogenic according to our data. Variant chr1-109231677-G-T is described in ClinVar as [no_classifications_from_unflagged_records]. Clinvar id is 1209576.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=1, Pathogenic=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SARS1 | NM_006513.4 | c.638G>T | p.Arg213Leu | missense_variant | 6/11 | ENST00000234677.7 | NP_006504.2 | |
SARS1 | NM_001330669.1 | c.638G>T | p.Arg213Leu | missense_variant | 6/12 | NP_001317598.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SARS1 | ENST00000234677.7 | c.638G>T | p.Arg213Leu | missense_variant | 6/11 | 1 | NM_006513.4 | ENSP00000234677 | P1 | |
SARS1 | ENST00000369923.4 | c.638G>T | p.Arg213Leu | missense_variant | 6/12 | 5 | ENSP00000358939 | |||
SARS1 | ENST00000471705.1 | n.520G>T | non_coding_transcript_exon_variant | 1/2 | 2 | |||||
SARS1 | ENST00000477544.5 | n.472+2105G>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: no classifications from unflagged records
Submissions summary: Pathogenic:2
Revision: no classifications from unflagged records
LINK: link
Submissions by phenotype
Neurodevelopmental disorder with microcephaly, ataxia, and seizures Pathogenic:2
Likely pathogenic, flagged submission | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | - | - - |
Pathogenic, flagged submission | literature only | OMIM | Jul 01, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Loss of MoRF binding (P = 0.1764);Loss of MoRF binding (P = 0.1764);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
No publications associated with this variant yet.