Variant 6-2678343-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001012418.5(MYLK4):c.917A>T(p.Asp306Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,796 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: 6.8e-7 ( 0 hom. )

Consequence

MYLK4
NM_001012418.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.98

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK4	NM_001012418.5 linkuse as main transcript	c.917A>T	p.Asp306Val	missense_variant	10/13	ENST00000274643.9	NP_001012418.2
MYLK4	NM_001347872.2 linkuse as main transcript	c.1085A>T	p.Asp362Val	missense_variant	10/13		NP_001334801.1	Q86YV6A0A8V8TMV3
MYLK4	XM_005249078.5 linkuse as main transcript	c.1160A>T	p.Asp387Val	missense_variant	10/13		XP_005249135.2
MYLK4	XM_006715082.4 linkuse as main transcript	c.899A>T	p.Asp300Val	missense_variant	9/12		XP_006715145.1	A0A2R8Y4U5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYLK4	ENST00000274643.9 linkuse as main transcript	c.917A>T	p.Asp306Val	missense_variant	10/13	1	NM_001012418.5	ENSP00000274643.7	Q86YV6-1
MYLK4	ENST00000698899.1 linkuse as main transcript	c.1085A>T	p.Asp362Val	missense_variant	10/13			ENSP00000514016.1	A0A8V8TMV3
MYLK4	ENST00000647417.1 linkuse as main transcript	c.899A>T	p.Asp300Val	missense_variant	9/12			ENSP00000494309.1	A0A2R8Y4U5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251402

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727200

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 05, 2021

The c.917A>T (p.D306V) alteration is located in exon 10 (coding exon 9) of the MYLK4 gene. This alteration results from a A to T substitution at nucleotide position 917, causing the aspartic acid (D) at amino acid position 306 to be replaced by a valine (V). 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

Benign

0.29

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-0.30

MutationAssessor

Benign

2.0

.;M

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.8

.;D

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0010

.;D

Polyphen

0.99

.;D

Vest4

0.84

MutPred

0.62

.;Loss of solvent accessibility (P = 0.0098);

MVP

0.69

MPC

0.77

ClinPred

0.99

GERP RS

5.0

Varity_R

0.73

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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