Genetic Variant MYH10:c.1958-3577A>G (chr17-8524862-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001256012.3(MYH10):c.1958-3577A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 152,328 control chromosomes in the GnomAD database, including 70,892 homozygotes. 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 0.96 ( 70892 hom., cov: 32)

Consequence

MYH10
NM_001256012.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.944

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

MYH10-related neurodevelopmental disorder with congenital anomalies
Inheritance: AD Classification: MODERATE Submitted by: G2P
coloboma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

MYH10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH10	NM_001256012.3 link	c.1958-3577A>G	intron_variant	Intron 17 of 42	ENST00000360416.8	NP_001242941.1	P35580-4G1UI33
MYH10	NM_001375266.1 link	c.1895-3577A>G	intron_variant	Intron 16 of 41		NP_001362195.1
MYH10	NM_001256095.2 link	c.1892-3577A>G	intron_variant	Intron 16 of 41		NP_001243024.1	P35580-5
MYH10	NM_005964.5 link	c.1865-3577A>G	intron_variant	Intron 15 of 40		NP_005955.3	P35580-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH10	ENST00000360416.8 link	c.1958-3577A>G		intron_variant	Intron 17 of 42	1	NM_001256012.3	ENSP00000353590.4		P35580-4

Frequencies

GnomAD3 genomes

AF:

0.963

AC:

146585

AN:

152210

Hom.:

70839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.872

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.984

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.976

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.963

AC:

146697

AN:

152328

Hom.:

70892

Cov.:

AF XY:

0.964

AC XY:

71831

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.872

AC:

36238

AN:

41544

American (AMR)

AF:

0.984

AC:

15066

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5186

AN:

5186

South Asian (SAS)

AF:

1.00

AC:

4822

AN:

4824

European-Finnish (FIN)

AF:

1.00

AC:

10628

AN:

10628

Middle Eastern (MID)

AF:

0.993

AC:

292

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68016

AN:

68040

Other (OTH)

AF:

0.976

AC:

2065

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

250

499

749

998

1248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.972

Hom.:

10646

Bravo

AF:

0.958

Asia WGS

AF:

0.994

AC:

3456

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.93

(source)

DANN

Benign

0.68

PhyloP100

-0.94

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over