1-109230944-G-T

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM5 PP3_Moderate

The NM_006513.4(SARS1):​c.514G>T​(p.Asp172Tyr) 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. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D172N) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SARS1 NM_006513.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-109230944-G-A is described in ClinVar as [no_classifications_from_unflagged_records]. Clinvar id is 440921.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1}.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARS1	NM_006513.4	c.514G>T	p.Asp172Tyr	missense_variant	Exon 5 of 11	ENST00000234677.7	NP_006504.2
SARS1	NM_001330669.1	c.514G>T	p.Asp172Tyr	missense_variant	Exon 5 of 12		NP_001317598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARS1	ENST00000234677.7	c.514G>T	p.Asp172Tyr	missense_variant	Exon 5 of 11	1	NM_006513.4	ENSP00000234677.2
SARS1	ENST00000369923.4	c.514G>T	p.Asp172Tyr	missense_variant	Exon 5 of 12	5		ENSP00000358939.4
SARS1	ENST00000477544.5	n.472+1372G>T		intron_variant	Intron 4 of 4	2
SARS1	ENST00000471705.1	n.-214G>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.64	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-8.4	D;D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.95
MutPred		0.49		Gain of phosphorylation at D172 (P = 0.0563);Gain of phosphorylation at D172 (P = 0.0563);
MVP		0.84
MPC		2.0
ClinPred		1.0	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.96

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: chr1-109773566;