17-47222448-A-T

Position:

chr17-47222448-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002476.2(MYL4):c.556A>T(p.Asn186Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,084 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 20 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 18 hom. )

Consequence

MYL4
NM_002476.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 7.33

Variant links:

Genes affected

MYL4 (HGNC:7585): (myosin light chain 4) Myosin is a hexameric ATPase cellular motor protein. It is composed of two myosin heavy chains, two nonphosphorylatable myosin alkali light chains, and two phosphorylatable myosin regulatory light chains. This gene encodes a myosin alkali light chain that is found in embryonic muscle and adult atria. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

MYL4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014120817).

BP6

Variant 17-47222448-A-T is Benign according to our data. Variant chr17-47222448-A-T is described in ClinVar as [Benign]. Clinvar id is 476210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00763 (1161/152244) while in subpopulation AFR AF= 0.0271 (1125/41528). AF 95% confidence interval is 0.0258. There are 20 homozygotes in gnomad4. There are 563 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1161 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL4	NM_002476.2 linkuse as main transcript	c.556A>T	p.Asn186Tyr	missense_variant	5/7	ENST00000393450.5	NP_002467.1	P12829

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL4	ENST00000393450.5 linkuse as main transcript	c.556A>T	p.Asn186Tyr	missense_variant	5/7	1	NM_002476.2	ENSP00000377096.1		P12829

Frequencies

GnomAD3 genomes

AF:

0.00763

AC:

1160

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0271

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

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:

0.0000294

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00184

AC:

463

AN:

251358

Hom.:

AF XY:

0.00132

AC XY:

179

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0268

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000733

AC:

1072

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

470

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0273

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.00763

AC:

1161

AN:

152244

Hom.:

Cov.:

AF XY:

0.00756

AC XY:

563

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0271

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.000501

Hom.:

Bravo

AF:

0.00865

ESP6500AA

AF:

0.0234

AC:

103

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00236

AC:

286

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2020	- -

Atrial fibrillation, familial, 18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

MYL4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

D;D;.;D

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

.;D;D;.

MetaRNN

Benign

0.014

T;T;T;T

MetaSVM

Uncertain

0.58

MutationAssessor

Pathogenic

4.0

H;H;.;H

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.4

.;D;.;D

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

.;D;.;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.85

MVP

0.96

MPC

0.71

ClinPred

0.12

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.58

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