chr1-109231677-G-T

Variant names:

• chr1-109231677-G-T
• rs539161490
• NM_006513.4:c.638G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

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).

• 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
• Publications: 0 publications found

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]

SARS1 Gene-Disease associations (from GenCC):

• hereditary peripheral neuropathy

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• neurodevelopmental disorder

  Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, G2P
• neurodevelopmental disorder with microcephaly, ataxia, and seizures

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006513.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARS1	NM_006513.4	MANE Select	c.638G>T	p.Arg213Leu	missense	Exon 6 of 11	NP_006504.2
	SARS1	NM_001330669.1		c.638G>T	p.Arg213Leu	missense	Exon 6 of 12	NP_001317598.1	Q5T5C7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARS1	ENST00000234677.7	TSL:1 MANE Select	c.638G>T	p.Arg213Leu	missense	Exon 6 of 11	ENSP00000234677.2	P49591
	SARS1	ENST00000943750.1		c.755G>T	p.Arg252Leu	missense	Exon 7 of 13	ENSP00000613809.1
	SARS1	ENST00000943751.1		c.755G>T	p.Arg252Leu	missense	Exon 7 of 12	ENSP00000613810.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: no classifications from unflagged records

Revision: no classifications from unflagged records

Pathogenic	VUS	Benign	Condition
2	-	-	Neurodevelopmental disorder with microcephaly, ataxia, and seizures (2)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.54
Sift	Benign	0.077	T
Sift4G	Benign	0.15	T
Polyphen		0.69	P
Vest4		0.60
MutPred		0.66		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
Mutation Taster		=37/63	disease causing

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

Other links and lift over

dbSNP: rs539161490; hg19: chr1-109774299;