NM_006513.4:c.514G>A

Variant names:

• chr1-109230944-G-A
• rs1553178049
• NM_006513.4:c.514G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006513.4(SARS1):​c.514G>A​(p.Asp172Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as no classifications from unflagged records (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SARS1 NM_006513.4 missense
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:1
• Conservation: PhyloP100: 9.72
• 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):

• neurodevelopmental disorder with microcephaly, ataxia, and seizures

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARS1	NM_006513.4	MANE Select	c.514G>A	p.Asp172Asn	missense	Exon 5 of 11	NP_006504.2
	SARS1	NM_001330669.1		c.514G>A	p.Asp172Asn	missense	Exon 5 of 12	NP_001317598.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARS1	ENST00000234677.7	TSL:1 MANE Select	c.514G>A	p.Asp172Asn	missense	Exon 5 of 11	ENSP00000234677.2
	SARS1	ENST00000369923.4	TSL:5	c.514G>A	p.Asp172Asn	missense	Exon 5 of 12	ENSP00000358939.4
	SARS1	ENST00000477544.5	TSL:2	n.472+1372G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: no classifications from unflagged records

Submissions summary: Pathogenic:1

Revision: no classifications from unflagged records

Submissions by phenotype

Neurodevelopmental disorder with microcephaly, ataxia, and seizures Pathogenic:1

Jul 01, 2022

OMIM

Significance: Pathogenic

Review Status: flagged submission

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.44	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		9.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.45		Gain of MoRF binding (P = 0.0512)
MVP		0.85
MPC		1.8
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.69
gMVP		0.91
Mutation Taster		=1/99	disease causing (ClinVar)

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: rs1553178049; hg19: chr1-109773566;