1-109228386-C-T

Position:

• chr1-109228386-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_006513.4(SARS1):​c.242C>T​(p.Pro81Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SARS1 NM_006513.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.34

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SARS1. . Gene score misZ 2.6571 (greater than the threshold 3.09). Trascript score misZ 3.2534 (greater than threshold 3.09). GenCC has associacion of gene with autosomal recessive non-syndromic intellectual disability, neurodevelopmental disorder with microcephaly, ataxia, and seizures.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SARS1	NM_006513.4	c.242C>T	p.Pro81Leu	missense_variant	3/11	ENST00000234677.7	NP_006504.2
SARS1	NM_001330669.1	c.242C>T	p.Pro81Leu	missense_variant	3/12		NP_001317598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SARS1	ENST00000234677.7	c.242C>T	p.Pro81Leu	missense_variant	3/11	1	NM_006513.4	ENSP00000234677	P1
SARS1	ENST00000369923.4	c.242C>T	p.Pro81Leu	missense_variant	3/12	5		ENSP00000358939
SARS1	ENST00000477544.5	n.267C>T		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 01, 2023

The c.242C>T (p.P81L) alteration is located in exon 3 (coding exon 3) of the SARS gene. This alteration results from a C to T substitution at nucleotide position 242, causing the proline (P) at amino acid position 81 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.62	D;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Uncertain	0.46
Sift	Benign	0.050	D;D
Sift4G	Uncertain	0.059	T;T
Polyphen		0.76	P;P
Vest4		0.65
MutPred		0.45		Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);
MVP		0.55
MPC		0.82
ClinPred		0.99	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.62

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: chr1-109771008;