dbSNP rs4791716: 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

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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