1-109229463-C-T

Variant names:

• chr1-109229463-C-T
• rs1472705384
• NM_006513.4:c.338C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006513.4(SARS1):​c.338C>T​(p.Ala113Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A113G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SARS1 NM_006513.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.85
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.338C>T	p.Ala113Val	missense	Exon 4 of 11	NP_006504.2
	SARS1	NM_001330669.1		c.338C>T	p.Ala113Val	missense	Exon 4 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.338C>T	p.Ala113Val	missense	Exon 4 of 11	ENSP00000234677.2	P49591
	SARS1	ENST00000943750.1		c.455C>T	p.Ala152Val	missense	Exon 5 of 13	ENSP00000613809.1
	SARS1	ENST00000943751.1		c.455C>T	p.Ala152Val	missense	Exon 5 of 12	ENSP00000613810.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251408 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.17
Sift	Benign	0.067	T
Sift4G	Benign	0.15	T
Polyphen		0.035	B
Vest4		0.78
MutPred		0.54		Loss of sheet (P = 0.007)
MVP		0.46
MPC		0.79
ClinPred		0.51	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.46
gMVP		0.55
Mutation Taster		=7/93	disease causing

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: rs1472705384; hg19: chr1-109772085;