1-32775672-CTG-C

Position:

• chr1-32775672-CTG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003680.4(YARS1):​c.*307_*308del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 410,384 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: YARS1 NM_003680.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.693

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-32775672-CTG-C is Benign according to our data. Variant chr1-32775672-CTG-C is described in ClinVar as [Likely_benign]. Clinvar id is 297143.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00135 (205/152288) while in subpopulation NFE AF= 0.00216 (147/68026). AF 95% confidence interval is 0.00188. There are 1 homozygotes in gnomad4. There are 98 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YARS1	NM_003680.4	c.*307_*308del		3_prime_UTR_variant	13/13	ENST00000373477.9	NP_003671.1
YARS1	XM_011542347.3	c.*307_*308del		3_prime_UTR_variant	11/11		XP_011540649.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YARS1	ENST00000373477.9	c.*307_*308del		3_prime_UTR_variant	13/13	1	NM_003680.4	ENSP00000362576	P1

Frequencies

GnomAD3 genomes AF: 0.00134 AC: 204 AN: 152170 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.00135 AC: 349 AN: 258096 Hom.: 2 AF XY: 0.00124 AC XY: 167 AN XY: 134654

Gnomad4 AFR exome AF: 0.000114

Gnomad4 AMR exome AF: 0.000521

Gnomad4 ASJ exome AF: 0.000124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000441

Gnomad4 FIN exome AF: 0.00207

Gnomad4 NFE exome AF: 0.00181

Gnomad4 OTH exome AF: 0.00122

GnomAD4 genome AF: 0.00135 AC: 205 AN: 152288 Hom.: 1 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74462

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.00216

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00178 Hom.: 0

Bravo AF: 0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth, Intermediate Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs372462149; hg19: chr1-33241273;