16-75628322-C-T

Position:

• chr16-75628322-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005548.3(KARS1):​c.1695+247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,200 control chromosomes in the GnomAD database, including 3,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (3004 hom., cov: 33)
• Consequence: KARS1 NM_005548.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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]

KARS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-75628322-C-T is Benign according to our data. Variant chr16-75628322-C-T is described in ClinVar as [Benign]. Clinvar id is 1293602.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KARS1	NM_005548.3	c.1695+247G>A		intron_variant		ENST00000302445.8	NP_005539.1
KARS1	NM_001130089.2	c.1779+247G>A		intron_variant			NP_001123561.1
KARS1	NM_001378148.1	c.1227+247G>A		intron_variant			NP_001365077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KARS1	ENST00000302445.8	c.1695+247G>A		intron_variant		1	NM_005548.3	ENSP00000303043.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20325 AN: 152082 Hom.: 3001 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.0505

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.134 AC: 20365 AN: 152200 Hom.: 3004 Cov.: 33 AF XY: 0.130 AC XY: 9661 AN XY: 74446

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.0542

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.00501

Gnomad4 SAS AF: 0.0505

Gnomad4 FIN AF: 0.0642

Gnomad4 NFE AF: 0.0412

Gnomad4 OTH AF: 0.0934

Alfa AF: 0.0867 Hom.: 408

Bravo AF: 0.143

Asia WGS AF: 0.0530 AC: 185 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

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.034
DANN	Benign	0.46

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: rs8051771; hg19: chr16-75662220;