16-75628381-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005548.3(KARS1):c.1695+187del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 152,276 control chromosomes in the GnomAD database, including 119 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.032 (119 hom., cov: 32)
• Consequence: KARS1 NM_005548.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.542

Genes affected

KARS1 (HGNC:6215): (lysyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Lysyl-tRNA synthetase is a homodimer localized to the cytoplasm which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-75628381-AG-A is Benign according to our data. Variant chr16-75628381-AG-A is described in ClinVar as [Benign]. Clinvar id is 1182881.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KARS1	NM_005548.3	c.1695+187del		intron_variant		ENST00000302445.8
KARS1	NM_001130089.2	c.1779+187del		intron_variant
KARS1	NM_001378148.1	c.1227+187del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KARS1	ENST00000302445.8	c.1695+187del		intron_variant		1	NM_005548.3	A1

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 4894 AN: 152158 Hom.: 118 Cov.: 32

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.00594

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0321

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0322 AC: 4898 AN: 152276 Hom.: 119 Cov.: 32 AF XY: 0.0318 AC XY: 2368 AN XY: 74450

Gnomad4 AFR AF: 0.0669

Gnomad4 AMR AF: 0.0186

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0304

Gnomad4 SAS AF: 0.0571

Gnomad4 FIN AF: 0.00594

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.0244 Hom.: 12

Bravo AF: 0.0342

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

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: rs5817957; hg19: chr16-75662279;