6-2728366-T-C

Variant names:

• chr6-2728366-T-C
• rs4246059
• NM_001012418.5:c.159+20770A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012418.5(MYLK4):​c.159+20770A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,762 control chromosomes in the GnomAD database, including 23,748 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23748 hom., cov: 31)
• Consequence: MYLK4 NM_001012418.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 2 publications found

Genes affected

MYLK4 (HGNC:27972): (myosin light chain kinase family member 4) Predicted to enable myosin light chain kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK4	NM_001012418.5	c.159+20770A>G		intron_variant	Intron 2 of 12	ENST00000274643.9	NP_001012418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK4	ENST00000274643.9	c.159+20770A>G		intron_variant	Intron 2 of 12	1	NM_001012418.5	ENSP00000274643.7
MYLK4	ENST00000698899.1	c.327+20770A>G		intron_variant	Intron 2 of 12			ENSP00000514016.1
MYLK4	ENST00000647417.1	c.141+15530A>G		intron_variant	Intron 1 of 11			ENSP00000494309.1
MYLK4	ENST00000698900.1	n.420+20770A>G		intron_variant	Intron 3 of 8

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82293 AN: 151650 Hom.: 23748 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.542 AC: 82313 AN: 151762 Hom.: 23748 Cov.: 31 AF XY: 0.547 AC XY: 40529 AN XY: 74110

African (AFR) AF: 0.349 AC: 14440 AN: 41396

American (AMR) AF: 0.586 AC: 8935 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3468

East Asian (EAS) AF: 0.823 AC: 4253 AN: 5168

South Asian (SAS) AF: 0.621 AC: 2989 AN: 4814

European-Finnish (FIN) AF: 0.627 AC: 6543 AN: 10436

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41596 AN: 67912

Other (OTH) AF: 0.537 AC: 1130 AN: 2106

Alfa AF: 0.589 Hom.: 83824

Bravo AF: 0.533

Asia WGS AF: 0.676 AC: 2349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.075
DANN	Benign	0.57
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4246059; hg19: chr6-2728600;