1-109231677-G-T

Variant names:

• chr1-109231677-G-T
• NM_006513.4:c.638G>T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PS1_Moderate PM2 PP5

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 the same amino acid substitution has been previously reported as Likely pathogenic in UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SARS1 NM_006513.4 missense
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:2
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 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
• 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 rank	MANE	Protein	UniProt
SARS1	NM_006513.4	c.638G>T	p.Arg213Leu	missense_variant	Exon 6 of 11	ENST00000234677.7	NP_006504.2
SARS1	NM_001330669.1	c.638G>T	p.Arg213Leu	missense_variant	Exon 6 of 12		NP_001317598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARS1	ENST00000234677.7	c.638G>T	p.Arg213Leu	missense_variant	Exon 6 of 11	1	NM_006513.4	ENSP00000234677.2
SARS1	ENST00000369923.4	c.638G>T	p.Arg213Leu	missense_variant	Exon 6 of 12	5		ENSP00000358939.4
SARS1	ENST00000471705.1	n.520G>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
SARS1	ENST00000477544.5	n.472+2105G>T		intron_variant	Intron 4 of 4	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

Submissions by phenotype

Neurodevelopmental disorder with microcephaly, ataxia, and seizures Pathogenic:2

Jul 01, 2022

OMIM

Significance: Pathogenic

Review Status: flagged submission

Collection Method: literature only

- -

-

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

Significance: Likely pathogenic

Review Status: flagged submission

Collection Method: clinical testing

- -

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;.
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;