Variant 1-203170428-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004997.3(MYBPH):c.956G>A(p.Arg319His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,614,048 control chromosomes in the GnomAD database, including 7 homozygotes. 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: 𝑓 0.0012 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 5 hom. )

Consequence

MYBPH
NM_004997.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

MYBPH (HGNC:7552): (myosin binding protein H) Predicted to be a structural constituent of muscle. Predicted to be involved in regulation of striated muscle contraction. Predicted to be located in myosin filament. [provided by Alliance of Genome Resources, Apr 2022]

MYBPH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010614991).

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPH	NM_004997.3 linkuse as main transcript	c.956G>A	p.Arg319His	missense_variant	7/11	ENST00000255416.9
MYBPH	XM_047421205.1 linkuse as main transcript	c.1079G>A	p.Arg360His	missense_variant	8/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPH	ENST00000255416.9 linkuse as main transcript	c.956G>A	p.Arg319His	missense_variant	7/11	1	NM_004997.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

181

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00106

AC:

265

AN:

251168

Hom.:

AF XY:

0.00101

AC XY:

137

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00180

Gnomad NFE exome

AF:

0.00166

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.00144

AC:

2103

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1012

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.00163

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00121

AC:

184

AN:

152224

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.00121

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00128

AC:

155

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00119

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 18, 2021

The c.956G>A (p.R319H) alteration is located in exon 7 (coding exon 7) of the MYBPH gene. This alteration results from a G to A substitution at nucleotide position 956, causing the arginine (R) at amino acid position 319 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

Benign

0.15

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.55

Cadd

Benign

Dann

Benign

0.85

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.77

T;D

M_CAP

Benign

0.0050

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

Sift4G

Benign

1.0

T;T

Polyphen

0.0070

.;B

Vest4

0.19

MVP

0.72

MPC

0.17

ClinPred

0.0094

GERP RS

4.2

Varity_R

0.053

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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