Variant chr17-8475904-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_001256012.3(MYH10):c.5924G>T(p.Arg1975Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MYH10
NM_001256012.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.53

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity MYH10_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28332344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH10	NM_001256012.3 link	c.5924G>T	p.Arg1975Leu	missense_variant	Exon 43 of 43	ENST00000360416.8	NP_001242941.1	P35580-4G1UI33
MYH10	NM_001375266.1 link	c.5861G>T	p.Arg1954Leu	missense_variant	Exon 42 of 42		NP_001362195.1
MYH10	NM_001256095.2 link	c.5858G>T	p.Arg1953Leu	missense_variant	Exon 42 of 42		NP_001243024.1	P35580-5
MYH10	NM_005964.5 link	c.5831G>T	p.Arg1944Leu	missense_variant	Exon 41 of 41		NP_005955.3	P35580-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH10	ENST00000360416.8 link	c.5924G>T	p.Arg1975Leu	missense_variant	Exon 43 of 43	1	NM_001256012.3	ENSP00000353590.4		P35580-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727212

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

.;.;D

Eigen

Benign

-0.023

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.0

.;.;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.8

N;.;N

REVEL

Uncertain

0.45

Sift

Uncertain

0.0060

D;.;D

Sift4G

Uncertain

0.031

D;D;D

Polyphen

0.0

.;.;B

Vest4

0.49

MutPred

0.15

.;.;Loss of MoRF binding (P = 0.0234);

MVP

0.82

MPC

0.70

ClinPred

0.65

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.38

gMVP

0.53

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over