1-109228401-G-C

Position:

• chr1-109228401-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_006513.4(SARS1):​c.257G>C​(p.Ser86Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SARS1 NM_006513.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 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.
• BP4: Computational evidence support a benign effect (MetaRNN=0.1239295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SARS1	NM_006513.4	c.257G>C	p.Ser86Thr	missense_variant	3/11	ENST00000234677.7	NP_006504.2
SARS1	NM_001330669.1	c.257G>C	p.Ser86Thr	missense_variant	3/12		NP_001317598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SARS1	ENST00000234677.7	c.257G>C	p.Ser86Thr	missense_variant	3/11	1	NM_006513.4	ENSP00000234677.2
SARS1	ENST00000369923.4	c.257G>C	p.Ser86Thr	missense_variant	3/12	5		ENSP00000358939.4
SARS1	ENST00000477544.5	n.282G>C		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461442 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 727058

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Nov 10, 2024

The c.257G>C (p.S86T) alteration is located in exon 3 (coding exon 3) of the SARS gene. This alteration results from a G to C substitution at nucleotide position 257, causing the serine (S) at amino acid position 86 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.50
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.67
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.64	N;N
REVEL	Benign	0.19
Sift	Benign	0.51	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;B
Vest4		0.20
MutPred		0.49		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.45
MPC		0.68
ClinPred		0.074	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.17

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: chr1-109771023;