NM_006513.4:c.1326G>A

Variant names:

• chr1-109237312-G-A
• rs148902081
• NM_006513.4:c.1326G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_006513.4(SARS1):​c.1326G>A​(p.Glu442Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000548 in 1,614,216 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (3 hom.)
• Consequence: SARS1 NM_006513.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.82
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 1-109237312-G-A is Benign according to our data. Variant chr1-109237312-G-A is described in ClinVar as Benign. ClinVar VariationId is 732908.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00298 (454/152330) while in subpopulation AFR AF = 0.0103 (427/41576). AF 95% confidence interval is 0.00947. There are 6 homozygotes in GnomAd4. There are 206 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR,AD gene

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.1326G>A	p.Glu442Glu	synonymous	Exon 10 of 11	NP_006504.2
	SARS1	NM_001330669.1		c.1392G>A	p.Glu464Glu	synonymous	Exon 11 of 12	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.1326G>A	p.Glu442Glu	synonymous	Exon 10 of 11	ENSP00000234677.2	P49591
	SARS1	ENST00000943750.1		c.1509G>A	p.Glu503Glu	synonymous	Exon 12 of 13	ENSP00000613809.1
	SARS1	ENST00000943751.1		c.1443G>A	p.Glu481Glu	synonymous	Exon 11 of 12	ENSP00000613810.1

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 454 AN: 152212 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000855 AC: 215 AN: 251436 AF XY: 0.000567

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.000925

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000295 AC: 431 AN: 1461886 Hom.: 3 Cov.: 32 AF XY: 0.000250 AC XY: 182 AN XY: 727244

African (AFR) AF: 0.00911 AC: 305 AN: 33480

American (AMR) AF: 0.00121 AC: 54 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1112012

Other (OTH) AF: 0.000878 AC: 53 AN: 60396

GnomAD4 genome AF: 0.00298 AC: 454 AN: 152330 Hom.: 6 Cov.: 33 AF XY: 0.00277 AC XY: 206 AN XY: 74498

African (AFR) AF: 0.0103 AC: 427 AN: 41576

American (AMR) AF: 0.00111 AC: 17 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00162 Hom.: 0

Bravo AF: 0.00359

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.56
PhyloP100		5.8
Mutation Taster		=97/3	polymorphism

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: rs148902081; hg19: chr1-109779934;