Variant 6-2683078-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000274643.9(MYLK4):c.630G>C(p.Gln210His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,888 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

MYLK4
ENST00000274643.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

Variant links:

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]

MYLK4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK4	NM_001012418.5 linkuse as main transcript	c.630G>C	p.Gln210His	missense_variant	7/13	ENST00000274643.9	NP_001012418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK4	ENST00000274643.9 linkuse as main transcript	c.630G>C	p.Gln210His	missense_variant	7/13	1	NM_001012418.5	ENSP00000274643	A2	Q86YV6-1
MYLK4	ENST00000698899.1 linkuse as main transcript	c.798G>C	p.Gln266His	missense_variant	7/13			ENSP00000514016	A2
MYLK4	ENST00000647417.1 linkuse as main transcript	c.612G>C	p.Gln204His	missense_variant	6/12			ENSP00000494309	P2
MYLK4	ENST00000698900.1 linkuse as main transcript	n.891G>C		non_coding_transcript_exon_variant	8/9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2023

The c.630G>C (p.Q210H) alteration is located in exon 7 (coding exon 6) of the MYLK4 gene. This alteration results from a G to C substitution at nucleotide position 630, causing the glutamine (Q) at amino acid position 210 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

.;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.051

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Benign

-0.39

MutationAssessor

Pathogenic

2.9

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.0

.;D

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0010

.;D

Polyphen

1.0

.;D

Vest4

0.56

MutPred

0.94

.;Loss of ubiquitination at K209 (P = 0.2335);

MVP

0.55

MPC

0.59

ClinPred

0.99

GERP RS

3.8

Varity_R

0.91

gMVP

0.90

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

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