Variant chr3-123612296-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_053025.4(MYLK):c.*1809A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,564 control chromosomes in the GnomAD database, including 10,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 10377 hom., cov: 32)

Exomes 𝑓: 0.087 ( 1 hom. )

Consequence

MYLK
NM_053025.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.266

Variant links:

Genes affected

MYLK (HGNC:7590): (myosin light chain kinase) This gene, a muscle member of the immunoglobulin gene superfamily, encodes myosin light chain kinase which is a calcium/calmodulin dependent enzyme. This kinase phosphorylates myosin regulatory light chains to facilitate myosin interaction with actin filaments to produce contractile activity. This gene encodes both smooth muscle and nonmuscle isoforms. In addition, using a separate promoter in an intron in the 3' region, it encodes telokin, a small protein identical in sequence to the C-terminus of myosin light chain kinase, that is independently expressed in smooth muscle and functions to stabilize unphosphorylated myosin filaments. A pseudogene is located on the p arm of chromosome 3. Four transcript variants that produce four isoforms of the calcium/calmodulin dependent enzyme have been identified as well as two transcripts that produce two isoforms of telokin. Additional variants have been identified but lack full length transcripts. [provided by RefSeq, Jul 2008]

MYLK links:

MYLK-AS1 (HGNC:42440): (MYLK antisense RNA 1)

MYLK-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 3-123612296-T-C is Benign according to our data. Variant chr3-123612296-T-C is described in ClinVar as [Benign]. Clinvar id is 342823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK	NM_053025.4 linkuse as main transcript	c.*1809A>G		3_prime_UTR_variant	34/34	ENST00000360304.8
MYLK-AS1	NR_038266.2 linkuse as main transcript	n.290-17198T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK	ENST00000360304.8 linkuse as main transcript	c.*1809A>G		3_prime_UTR_variant	34/34	5	NM_053025.4	P4	Q15746-1
MYLK-AS1	ENST00000485162.5 linkuse as main transcript	n.261-17198T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46110

AN:

152008

Hom.:

10345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.616

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.0931

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.291

GnomAD4 exome

AF:

0.0868

AC:

AN:

438

Hom.:

Cov.:

AF XY:

0.106

AC XY:

AN XY:

264

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.0845

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.304

AC:

46200

AN:

152126

Hom.:

10377

Cov.:

AF XY:

0.304

AC XY:

22592

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.587

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.238

Gnomad4 EAS

AF:

0.617

Gnomad4 SAS

AF:

0.324

Gnomad4 FIN

AF:

0.0931

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.185

Hom.:

5540

Bravo

AF:

0.336

Asia WGS

AF:

0.450

AC:

1566

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Aortic aneurysm, familial thoracic 7

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 03, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

3.7

DANN

Benign

0.86

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over