chr1-109228441-T-C

Variant names:

• chr1-109228441-T-C
• rs683182
• NM_006513.4:c.288+9T>C

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.288+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 1,589,930 control chromosomes in the GnomAD database, including 483,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (39251 hom., cov: 32)
  • Exomes 𝑓: 0.78 (444225 hom.)
• Consequence: SARS1 NM_006513.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.623
• Publications: 25 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=-0.86).
• BP6: Variant 1-109228441-T-C is Benign according to our data. Variant chr1-109228441-T-C is described in ClinVar as Benign. ClinVar VariationId is 1327978.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.288+9T>C		intron	N/A	NP_006504.2
	SARS1	NM_001330669.1		c.288+9T>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.288+9T>C		intron	N/A	ENSP00000234677.2	P49591
	SARS1	ENST00000943750.1		c.405+9T>C		intron	N/A	ENSP00000613809.1
	SARS1	ENST00000943751.1		c.405+9T>C		intron	N/A	ENSP00000613810.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106853 AN: 151982 Hom.: 39240 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.783

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: 0.750

GnomAD2 exomes AF: 0.768 AC: 191370 AN: 249204 AF XY: 0.766

Gnomad AFR exome AF: 0.463

Gnomad AMR exome AF: 0.812

Gnomad ASJ exome AF: 0.857

Gnomad EAS exome AF: 0.899

Gnomad FIN exome AF: 0.776

Gnomad NFE exome AF: 0.796

Gnomad OTH exome AF: 0.787

GnomAD4 exome AF: 0.783 AC: 1125252 AN: 1437830 Hom.: 444225 Cov.: 25 AF XY: 0.780 AC XY: 559296 AN XY: 716830

African (AFR) AF: 0.456 AC: 15027 AN: 32980

American (AMR) AF: 0.810 AC: 35747 AN: 44156

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 22218 AN: 25928

East Asian (EAS) AF: 0.884 AC: 34919 AN: 39510

South Asian (SAS) AF: 0.662 AC: 56446 AN: 85316

European-Finnish (FIN) AF: 0.773 AC: 41242 AN: 53326

Middle Eastern (MID) AF: 0.750 AC: 4296 AN: 5730

European-Non Finnish (NFE) AF: 0.796 AC: 869212 AN: 1091316

Other (OTH) AF: 0.775 AC: 46145 AN: 59568

GnomAD4 genome AF: 0.703 AC: 106901 AN: 152100 Hom.: 39251 Cov.: 32 AF XY: 0.702 AC XY: 52158 AN XY: 74350

African (AFR) AF: 0.474 AC: 19662 AN: 41452

American (AMR) AF: 0.782 AC: 11961 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3021 AN: 3470

East Asian (EAS) AF: 0.893 AC: 4630 AN: 5182

South Asian (SAS) AF: 0.667 AC: 3207 AN: 4806

European-Finnish (FIN) AF: 0.765 AC: 8091 AN: 10574

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

European-Non Finnish (NFE) AF: 0.792 AC: 53831 AN: 68010

Other (OTH) AF: 0.753 AC: 1591 AN: 2114

Alfa AF: 0.768 Hom.: 100083

Bravo AF: 0.698

Asia WGS AF: 0.755 AC: 2624 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	-0.86
CADD	Benign	1.3
DANN	Benign	0.42
PhyloP100		-0.62
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: rs683182; hg19: chr1-109771063; COSMIC: COSV52320213; COSMIC: COSV52320213;