rs796052168

Variant names:

• chr6-2685390-C-T
• rs796052168
• NM_001012418.5:c.451G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-2685390-C-T
• chr6-2685390-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 6P and 1B. PM2 PP3_Strong BP6

The NM_001012418.5(MYLK4):​c.451G>A​(p.Glu151Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000385 in 1,556,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MYLK4 NM_001012418.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.91
• Publications: 4 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: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978
• BP6: Variant 6-2685390-C-T is Benign according to our data. Variant chr6-2685390-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 207879.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012418.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK4	NM_001012418.5	MANE Select	c.451G>A	p.Glu151Lys	missense	Exon 6 of 13	NP_001012418.2	Q86YV6-1
	MYLK4	NM_001347872.2		c.619G>A	p.Glu207Lys	missense	Exon 6 of 13	NP_001334801.1	A0A8V8TMV3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK4	ENST00000274643.9	TSL:1 MANE Select	c.451G>A	p.Glu151Lys	missense	Exon 6 of 13	ENSP00000274643.7	Q86YV6-1
	MYLK4	ENST00000698899.1		c.619G>A	p.Glu207Lys	missense	Exon 6 of 13	ENSP00000514016.1	A0A8V8TMV3
	MYLK4	ENST00000866488.1		c.451G>A	p.Glu151Lys	missense	Exon 7 of 14	ENSP00000536547.1

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 147636 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000300

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1409284 Hom.: 0 Cov.: 33 AF XY: 0.00000428 AC XY: 3 AN XY: 700540

African (AFR) AF: 0.00 AC: 0 AN: 31914

American (AMR) AF: 0.00 AC: 0 AN: 43082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24152

East Asian (EAS) AF: 0.00 AC: 0 AN: 35794

South Asian (SAS) AF: 0.00 AC: 0 AN: 85758

European-Finnish (FIN) AF: 0.0000205 AC: 1 AN: 48692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1077486

Other (OTH) AF: 0.0000176 AC: 1 AN: 56902

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 147636 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71998

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40584

American (AMR) AF: 0.00 AC: 0 AN: 14934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 4678

South Asian (SAS) AF: 0.00 AC: 0 AN: 4356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000300 AC: 2 AN: 66656

Other (OTH) AF: 0.00 AC: 0 AN: 2062

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		7.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.8	D
REVEL	Pathogenic	0.88
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.92		Gain of ubiquitination at E151 (P = 0.0146)
MVP		0.89
MPC		0.73
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.98
gMVP		0.94
Mutation Taster		=17/83	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs796052168; hg19: chr6-2685624; COSMIC: COSV51138552;