rs1553178049

Positions:

• chr1-109230944-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP2 PP3 PP5

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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SARS1 NM_006513.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.72

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.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SARS1
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807
• PP5: Variant 1-109230944-G-A is Pathogenic according to our data. Variant chr1-109230944-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 440921.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-109230944-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SARS1	NM_006513.4	c.514G>A	p.Asp172Asn	missense_variant	5/11	ENST00000234677.7
SARS1	NM_001330669.1	c.514G>A	p.Asp172Asn	missense_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SARS1	ENST00000234677.7	c.514G>A	p.Asp172Asn	missense_variant	5/11	1	NM_006513.4	P1
SARS1	ENST00000369923.4	c.514G>A	p.Asp172Asn	missense_variant	5/12	5
SARS1	ENST00000477544.5	n.472+1372G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Pathogenic	0.44	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Pathogenic	4.1	H;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		1.0	D;B
Vest4		0.85
MutPred		0.45		Gain of MoRF binding (P = 0.0512);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

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

LitVar

Other links and lift over

dbSNP: rs1553178049; hg19: chr1-109773566;