1-109235353-G-T

Variant names:

• chr1-109235353-G-T
• rs145465105
• NM_006513.4:c.891G>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS1

The NM_006513.4(SARS1):​c.891G>T​(p.Leu297Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000642 in 1,614,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00069 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (1 hom.)
• Consequence: SARS1 NM_006513.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.66
• Publications: 2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 1-109235353-G-T is Benign according to our data. Variant chr1-109235353-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 714605.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.66 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00069 (105/152266) while in subpopulation NFE AF = 0.00132 (90/68022). AF 95% confidence interval is 0.0011. There are 0 homozygotes in GnomAd4. There are 46 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.891G>T	p.Leu297Leu	synonymous	Exon 7 of 11	NP_006504.2
	SARS1	NM_001330669.1		c.891G>T	p.Leu297Leu	synonymous	Exon 7 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.891G>T	p.Leu297Leu	synonymous	Exon 7 of 11	ENSP00000234677.2	P49591
	SARS1	ENST00000943750.1		c.1008G>T	p.Leu336Leu	synonymous	Exon 8 of 13	ENSP00000613809.1
	SARS1	ENST00000943751.1		c.1008G>T	p.Leu336Leu	synonymous	Exon 8 of 12	ENSP00000613810.1

Frequencies

GnomAD3 genomes AF: 0.000690 AC: 105 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.000497 AC: 125 AN: 251386 AF XY: 0.000449

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.000800

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000638 AC: 932 AN: 1461862 Hom.: 1 Cov.: 32 AF XY: 0.000650 AC XY: 473 AN XY: 727228

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000514 AC: 23 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000337 AC: 18 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000758 AC: 843 AN: 1112012

Other (OTH) AF: 0.000729 AC: 44 AN: 60396

GnomAD4 genome AF: 0.000690 AC: 105 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.000618 AC XY: 46 AN XY: 74450

African (AFR) AF: 0.0000963 AC: 4 AN: 41548

American (AMR) AF: 0.000458 AC: 7 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00132 AC: 90 AN: 68022

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.000442

EpiCase AF: 0.000763

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SARS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		1.7
Mutation Taster		=100/0	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: rs145465105; hg19: chr1-109777975;