3-123612593-A-ATAT

Position:

• chr3-123612593-A-ATAT

Variant summary

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

The NM_053025.4(MYLK):​c.*1511_*1512insATA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00925 in 152,348 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (21 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYLK NM_053025.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.673

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-123612593-A-ATAT is Benign according to our data. Variant chr3-123612593-A-ATAT is described in ClinVar as [Likely_benign]. Clinvar id is 342830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00925 (1409/152348) while in subpopulation AFR AF= 0.0317 (1318/41580). AF 95% confidence interval is 0.0303. There are 21 homozygotes in gnomad4. There are 676 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK	NM_053025.4	c.*1511_*1512insATA		3_prime_UTR_variant	34/34	ENST00000360304.8
MYLK-AS1	NR_038266.2	n.290-16899_290-16897dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK	ENST00000360304.8	c.*1511_*1512insATA		3_prime_UTR_variant	34/34	5	NM_053025.4	P4
MYLK-AS1	ENST00000485162.5	n.261-16899_261-16897dup		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00912 AC: 1388 AN: 152230 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00766

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 260

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00925 AC: 1409 AN: 152348 Hom.: 21 Cov.: 32 AF XY: 0.00907 AC XY: 676 AN XY: 74512

Gnomad4 AFR AF: 0.0317

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00961 Hom.: 0

Bravo AF: 0.0108

Asia WGS AF: 0.00318 AC: 11 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs140529334; hg19: chr3-123331440;