Variant 17-8475843-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001256012.3(MYH10):c.5985C>T(p.Thr1995=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000408 in 1,614,180 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 3 hom. )

Consequence

MYH10
NM_001256012.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.17

Variant links:

Genes affected

MYH10 (HGNC:7568): (myosin heavy chain 10) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-10 (MYO10). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene have been associated with May-Hegglin anomaly and developmental defects in brain and heart. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MYH10 links:

NDEL1 (HGNC:17620): (nudE neurodevelopment protein 1 like 1) Enables identical protein binding activity. Involved in chromosome segregation; positive regulation of GTPase activity; and regulation of intracellular protein transport. Located in kinetochore. Biomarker of schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

NDEL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 17-8475843-G-A is Benign according to our data. Variant chr17-8475843-G-A is described in ClinVar as [Benign]. Clinvar id is 712206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYH10	NM_001256012.3 linkuse as main transcript	c.5985C>T	p.Thr1995=	synonymous_variant	43/43	ENST00000360416.8	NP_001242941.1
MYH10	NM_001375266.1 linkuse as main transcript	c.5922C>T	p.Thr1974=	synonymous_variant	42/42		NP_001362195.1
MYH10	NM_001256095.2 linkuse as main transcript	c.5919C>T	p.Thr1973=	synonymous_variant	42/42		NP_001243024.1
MYH10	NM_005964.5 linkuse as main transcript	c.5892C>T	p.Thr1964=	synonymous_variant	41/41		NP_005955.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH10	ENST00000360416.8 linkuse as main transcript	c.5985C>T	p.Thr1995=	synonymous_variant	43/43	1	NM_001256012.3	ENSP00000353590		P35580-4

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

337

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000597

AC:

150

AN:

251446

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00837

Gnomad AMR exome

AF:

0.000289

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000215

AC:

314

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

166

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00762

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152296

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00787

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.00247

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

MYH10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 2019

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.0

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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