Variant 6-2678275-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001012418.5(MYLK4):c.985G>T(p.Asp329Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

MYLK4
NM_001012418.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33190033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYLK4	NM_001012418.5 linkuse as main transcript	c.985G>T	p.Asp329Tyr	missense_variant	10/13	ENST00000274643.9
MYLK4	NM_001347872.2 linkuse as main transcript	c.1153G>T	p.Asp385Tyr	missense_variant	10/13
MYLK4	XM_005249078.5 linkuse as main transcript	c.1228G>T	p.Asp410Tyr	missense_variant	10/13
MYLK4	XM_006715082.4 linkuse as main transcript	c.967G>T	p.Asp323Tyr	missense_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK4	ENST00000274643.9 linkuse as main transcript	c.985G>T	p.Asp329Tyr	missense_variant	10/13	1	NM_001012418.5	A2	Q86YV6-1
MYLK4	ENST00000698899.1 linkuse as main transcript	c.1153G>T	p.Asp385Tyr	missense_variant	10/13			A2
MYLK4	ENST00000647417.1 linkuse as main transcript	c.967G>T	p.Asp323Tyr	missense_variant	9/12			P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

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:

0.00

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 16, 2022

The c.985G>T (p.D329Y) alteration is located in exon 10 (coding exon 9) of the MYLK4 gene. This alteration results from a G to T substitution at nucleotide position 985, causing the aspartic acid (D) at amino acid position 329 to be replaced by a tyrosine (Y). 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

0.096

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

.;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.052

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.86

.;L

MutationTaster

Benign

0.89

D;D

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-4.8

.;D

REVEL

Benign

0.25

Sift

Benign

0.038

.;D

Sift4G

Uncertain

0.013

.;D

Polyphen

0.94

.;P

Vest4

0.65

MutPred

0.35

.;Loss of disorder (P = 0.0226);

MVP

0.72

MPC

0.62

ClinPred

0.96

GERP RS

4.1

Varity_R

0.30

gMVP

0.77

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