rs147538442

Variant names:

• chr1-32817193-G-A
• rs147538442
• NM_003680.4:c.52C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_003680.4(YARS1):​c.52C>T​(p.Leu18Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,614,214 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L18L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0020 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: YARS1 NM_003680.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.74
• Publications: 0 publications found

Genes affected

YARS1 (HGNC:12840): (tyrosyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Tyrosyl-tRNA synthetase belongs to the class I tRNA synthetase family. Cytokine activities have also been observed for the human tyrosyl-tRNA synthetase, after it is split into two parts, an N-terminal fragment that harbors the catalytic site and a C-terminal fragment found only in the mammalian enzyme. The N-terminal fragment is an interleukin-8-like cytokine, whereas the released C-terminal fragment is an EMAP II-like cytokine. [provided by RefSeq, Jul 2008]

S100PBP (HGNC:25768): (S100P binding protein) This gene encodes a protein that was originally identified by its interaction with S100 calcium-binding protein P. Expression of this protein has been reported to be associated with pancreatic ductal adenocarcinoma. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 1-32817193-G-A is Benign according to our data. Variant chr1-32817193-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 289456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.74 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00202 (308/152364) while in subpopulation AFR AF = 0.00608 (253/41598). AF 95% confidence interval is 0.00547. There are 3 homozygotes in GnomAd4. There are 121 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003680.4. 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
	YARS1	NM_003680.4	MANE Select	c.52C>T	p.Leu18Leu	synonymous	Exon 1 of 13	NP_003671.1	P54577
	S100PBP	NM_001256121.2		c.-526G>A		upstream_gene	N/A	NP_001243050.1	A0A0S2Z5M0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YARS1	ENST00000373477.9	TSL:1 MANE Select	c.52C>T	p.Leu18Leu	synonymous	Exon 1 of 13	ENSP00000362576.4	P54577
	YARS1	ENST00000906066.1		c.52C>T	p.Leu18Leu	synonymous	Exon 1 of 14	ENSP00000576125.1
	YARS1	ENST00000918766.1		c.52C>T	p.Leu18Leu	synonymous	Exon 1 of 13	ENSP00000588825.1

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 307 AN: 152246 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000442 AC: 111 AN: 251334 AF XY: 0.000272

Gnomad AFR exome AF: 0.00572

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000238 AC: 348 AN: 1461850 Hom.: 2 Cov.: 31 AF XY: 0.000184 AC XY: 134 AN XY: 727230

African (AFR) AF: 0.00806 AC: 270 AN: 33480

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

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

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111986

Other (OTH) AF: 0.000811 AC: 49 AN: 60394

GnomAD4 genome AF: 0.00202 AC: 308 AN: 152364 Hom.: 3 Cov.: 33 AF XY: 0.00162 AC XY: 121 AN XY: 74508

African (AFR) AF: 0.00608 AC: 253 AN: 41598

American (AMR) AF: 0.00333 AC: 51 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00103 Hom.: 0

Bravo AF: 0.00302

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Charcot-Marie-Tooth disease dominant intermediate C (2)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		2.7
PromoterAI		0.0015	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
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: rs147538442; hg19: chr1-33282794;