Variant rs3752463 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002473.6(MYH9):c.1012+56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,611,550 control chromosomes in the GnomAD database, including 253,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19090 hom., cov: 32)

Exomes 𝑓: 0.56 ( 234843 hom. )

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.49

Variant links:

Genes affected

MYH9 (HGNC:7579): (myosin heavy chain 9) This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness. [provided by RefSeq, Dec 2011]

MYH9 links:

MYH9 (HGNC:):

MYH9 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 (BayesDel_noAF=-0.91).

BP6

Variant 22-36320164-G-A is Benign according to our data. Variant chr22-36320164-G-A is described in ClinVar as [Benign]. Clinvar id is 1289525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6 linkuse as main transcript	c.1012+56C>T		intron_variant		ENST00000216181.11	NP_002464.1	P35579-1A0A024R1N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11 linkuse as main transcript	c.1012+56C>T		intron_variant		1	NM_002473.6	ENSP00000216181.6		P35579-1

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72096

AN:

151522

Hom.:

19090

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.681

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.589

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.594

Gnomad OTH

AF:

0.497

GnomAD4 exome

AF:

0.558

AC:

814043

AN:

1459910

Hom.:

234843

AF XY:

0.553

AC XY:

401770

AN XY:

726348

show subpopulations

Gnomad4 AFR exome

AF:

0.256

Gnomad4 AMR exome

AF:

0.604

Gnomad4 ASJ exome

AF:

0.453

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.400

Gnomad4 FIN exome

AF:

0.598

Gnomad4 NFE exome

AF:

0.594

Gnomad4 OTH exome

AF:

0.523

GnomAD4 genome

AF:

0.476

AC:

72105

AN:

151640

Hom.:

19090

Cov.:

AF XY:

0.473

AC XY:

35043

AN XY:

74060

show subpopulations

Gnomad4 AFR

AF:

0.265

Gnomad4 AMR

AF:

0.575

Gnomad4 ASJ

AF:

0.469

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.364

Gnomad4 FIN

AF:

0.589

Gnomad4 NFE

AF:

0.594

Gnomad4 OTH

AF:

0.492

Alfa

AF:

0.548

Hom.:

2937

Bravo

AF:

0.466

Asia WGS

AF:

0.242

AC:

846

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Jun 24, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 86% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 80. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.15

DANN

Benign

0.41

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