1-109231677-G-T

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

Scores

2
12
5

Clinical Significance

no classifications from unflagged records no classifications from unflagged records P:2

Conservation

PhyloP100: 5.65
Variant links:
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]

Genome browser will be placed here

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
SARS1NM_006513.4 linkuse as main transcriptc.638G>T p.Arg213Leu missense_variant 6/11 ENST00000234677.7 NP_006504.2
SARS1NM_001330669.1 linkuse as main transcriptc.638G>T p.Arg213Leu missense_variant 6/12 NP_001317598.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SARS1ENST00000234677.7 linkuse as main transcriptc.638G>T p.Arg213Leu missense_variant 6/111 NM_006513.4 ENSP00000234677 P1
SARS1ENST00000369923.4 linkuse as main transcriptc.638G>T p.Arg213Leu missense_variant 6/125 ENSP00000358939
SARS1ENST00000471705.1 linkuse as main transcriptn.520G>T non_coding_transcript_exon_variant 1/22
SARS1ENST00000477544.5 linkuse as main transcriptn.472+2105G>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
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 submissionclinical testingEquipe Genetique des Anomalies du Developpement, Université de Bourgogne-- -
Pathogenic, flagged submissionliterature onlyOMIMJul 01, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.57
D;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.047
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Uncertain
2.8
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-4.3
D;D
REVEL
Uncertain
0.54
Sift
Benign
0.077
T;T
Sift4G
Benign
0.15
T;T
Polyphen
0.69
P;P
Vest4
0.60
MutPred
0.66
Loss of MoRF binding (P = 0.1764);Loss of MoRF binding (P = 0.1764);
MVP
0.65
MPC
1.1
ClinPred
0.98
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.49
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-109774299; API