rs16941301

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005548.3(KARS1):c.1079-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,614,092 control chromosomes in the GnomAD database, including 672 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 119 hom., cov: 32)

Exomes 𝑓: 0.021 ( 553 hom. )

Consequence

KARS1
NM_005548.3 splice_region, intron

Scores

Splicing: ADA: 0.0002188

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.551

Publications

7 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 89
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
leukoencephalopathy, progressive, infantile-onset, with or without deafness
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Charcot-Marie-Tooth disease recessive intermediate B
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

KARS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 16-75631596-G-A is Benign according to our data. Variant chr16-75631596-G-A is described in ClinVar as Benign. ClinVar VariationId is 226678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005548.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KARS1	NM_005548.3	MANE Select	c.1079-7C>T	splice_region intron	N/A	NP_005539.1	Q15046-1
KARS1	NM_001130089.2		c.1163-7C>T	splice_region intron	N/A	NP_001123561.1	Q15046-2
KARS1	NM_001378148.1		c.611-7C>T	splice_region intron	N/A	NP_001365077.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KARS1	ENST00000302445.8	TSL:1 MANE Select	c.1079-7C>T	splice_region intron	N/A	ENSP00000303043.3	Q15046-1
KARS1	ENST00000319410.9	TSL:1	c.1163-7C>T	splice_region intron	N/A	ENSP00000325448.5	Q15046-2
KARS1	ENST00000898534.1		c.1193-7C>T	splice_region intron	N/A	ENSP00000568593.1

Frequencies

GnomAD3 genomes

AF:

0.0322

AC:

4896

AN:

152168

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0670

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0188

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.0302

Gnomad SAS

AF:

0.0578

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.0320

GnomAD2 exomes

AF:

0.0268

AC:

6734

AN:

251356

AF XY:

0.0281

show subpopulations

Gnomad AFR exome

AF:

0.0690

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.0304

Gnomad EAS exome

AF:

0.0261

Gnomad FIN exome

AF:

0.00462

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.0231

GnomAD4 exome

AF:

0.0207

AC:

30231

AN:

1461806

Hom.:

553

Cov.:

AF XY:

0.0221

AC XY:

16054

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.0723

AC:

2421

AN:

33470

American (AMR)

AF:

0.0157

AC:

701

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0316

AC:

826

AN:

26136

East Asian (EAS)

AF:

0.0259

AC:

1027

AN:

39700

South Asian (SAS)

AF:

0.0661

AC:

5699

AN:

86254

European-Finnish (FIN)

AF:

0.00594

AC:

317

AN:

53410

Middle Eastern (MID)

AF:

0.0511

AC:

295

AN:

5768

European-Non Finnish (NFE)

AF:

0.0156

AC:

17397

AN:

1111952

Other (OTH)

AF:

0.0256

AC:

1548

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1909

3818

5726

7635

9544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

750

1500

2250

3000

3750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0322

AC:

4900

AN:

152286

Hom.:

119

Cov.:

AF XY:

0.0319

AC XY:

2377

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0670

AC:

2782

AN:

41532

American (AMR)

AF:

0.0188

AC:

287

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

109

AN:

3472

East Asian (EAS)

AF:

0.0303

AC:

157

AN:

5186

South Asian (SAS)

AF:

0.0572

AC:

276

AN:

4824

European-Finnish (FIN)

AF:

0.00593

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0163

AC:

1107

AN:

68026

Other (OTH)

AF:

0.0317

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

232

464

696

928

1160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0214

Hom.:

Bravo

AF:

0.0342

Asia WGS

AF:

0.0660

AC:

228

AN:

3478

EpiCase

AF:

0.0172

EpiControl

AF:

0.0177

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.3

(source)

DANN

Benign

0.61

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over