rs658092

Variant names:

• chr1-109235955-T-C
• rs658092
• NM_006513.4:c.970-22T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-109235955-T-C
• chr1-109235955-T-A
• chr1-109235955-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006513.4(SARS1):​c.970-22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 1,585,244 control chromosomes in the GnomAD database, including 483,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39737 hom., cov: 31)
  • Exomes 𝑓: 0.78 (443708 hom.)
• Consequence: SARS1 NM_006513.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.783
• Publications: 9 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):

• hereditary peripheral neuropathy

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• neurodevelopmental disorder

  Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, G2P
• neurodevelopmental disorder with microcephaly, ataxia, and seizures

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-109235955-T-C is Benign according to our data. Variant chr1-109235955-T-C is described in ClinVar as Benign. ClinVar VariationId is 1327979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARS1	NM_006513.4	MANE Select	c.970-22T>C		intron	N/A	NP_006504.2
	SARS1	NM_001330669.1		c.970-22T>C		intron	N/A	NP_001317598.1	Q5T5C7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARS1	ENST00000234677.7	TSL:1 MANE Select	c.970-22T>C		intron	N/A	ENSP00000234677.2	P49591
	SARS1	ENST00000943750.1		c.1087-22T>C		intron	N/A	ENSP00000613809.1
	SARS1	ENST00000943751.1		c.1087-22T>C		intron	N/A	ENSP00000613810.1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107866 AN: 151944 Hom.: 39725 Cov.: 31

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.753

GnomAD2 exomes AF: 0.769 AC: 175087 AN: 227618 AF XY: 0.768

Gnomad AFR exome AF: 0.487

Gnomad AMR exome AF: 0.814

Gnomad ASJ exome AF: 0.853

Gnomad EAS exome AF: 0.899

Gnomad FIN exome AF: 0.776

Gnomad NFE exome AF: 0.796

Gnomad OTH exome AF: 0.784

GnomAD4 exome AF: 0.784 AC: 1123335 AN: 1433182 Hom.: 443708 Cov.: 33 AF XY: 0.781 AC XY: 556665 AN XY: 712394

African (AFR) AF: 0.480 AC: 15546 AN: 32354

American (AMR) AF: 0.811 AC: 31862 AN: 39284

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 20725 AN: 24214

East Asian (EAS) AF: 0.884 AC: 34925 AN: 39522

South Asian (SAS) AF: 0.662 AC: 53784 AN: 81294

European-Finnish (FIN) AF: 0.774 AC: 40556 AN: 52430

Middle Eastern (MID) AF: 0.749 AC: 4163 AN: 5560

European-Non Finnish (NFE) AF: 0.797 AC: 875843 AN: 1099380

Other (OTH) AF: 0.777 AC: 45931 AN: 59144

GnomAD4 genome AF: 0.710 AC: 107917 AN: 152062 Hom.: 39737 Cov.: 31 AF XY: 0.708 AC XY: 52618 AN XY: 74324

African (AFR) AF: 0.498 AC: 20646 AN: 41448

American (AMR) AF: 0.786 AC: 12012 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3019 AN: 3468

East Asian (EAS) AF: 0.893 AC: 4621 AN: 5172

South Asian (SAS) AF: 0.668 AC: 3215 AN: 4814

European-Finnish (FIN) AF: 0.765 AC: 8092 AN: 10582

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53814 AN: 67980

Other (OTH) AF: 0.755 AC: 1591 AN: 2106

Alfa AF: 0.747 Hom.: 8861

Bravo AF: 0.706

Asia WGS AF: 0.758 AC: 2634 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Neurodevelopmental disorder with microcephaly, ataxia, and seizures (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs658092; hg19: chr1-109778577; COSMIC: COSV52320257; COSMIC: COSV52320257;