Variant chr17-10443385-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017533.2(MYH4):c.5810G>A(p.Ser1937Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000021 ( 0 hom. )

Consequence

MYH4
NM_017533.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.165

Variant links:

Genes affected

MYH4 (HGNC:7574): (myosin heavy chain 4) Enables double-stranded RNA binding activity. Involved in muscle contraction. Located in myofibril. [provided by Alliance of Genome Resources, Apr 2022]

MYH4 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08383882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYH4	NM_017533.2 linkuse as main transcript	c.5810G>A	p.Ser1937Asn	missense_variant	40/40	ENST00000255381.2
MYHAS	NR_125367.1 linkuse as main transcript	n.167+37147C>T		intron_variant, non_coding_transcript_variant
MYH4	XM_017024676.2 linkuse as main transcript	c.5810G>A	p.Ser1937Asn	missense_variant	38/38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MYH4	ENST00000255381.2 linkuse as main transcript	c.5810G>A	p.Ser1937Asn	missense_variant	40/40	1	NM_017533.2	P1
	ENST00000399342.6 linkuse as main transcript	n.206+37108C>T		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1 linkuse as main transcript	n.143+37147C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461656

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727140

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Apr 05, 2023

The c.5810G>A (p.S1937N) alteration is located in exon 40 (coding exon 38) of the MYH4 gene. This alteration results from a G to A substitution at nucleotide position 5810, causing the serine (S) at amino acid position 1937 to be replaced by an asparagine (N). 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

0.097

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.11

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.79

M_CAP

Benign

0.020

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.090

REVEL

Benign

0.29

Sift

Benign

0.34

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.095

MutPred

0.14

Loss of phosphorylation at S1937 (P = 0.0298);

MVP

0.73

MPC

0.15

ClinPred

0.073

GERP RS

4.2

Varity_R

0.036

gMVP

0.071

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