Variant 17-8478334-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001256012.3(MYH10):c.5706+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,613,134 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 57 hom. )

Consequence

MYH10
NM_001256012.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.00004171

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.84

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-8478334-G-A is Benign according to our data. Variant chr17-8478334-G-A is described in ClinVar as [Benign]. Clinvar id is 770441.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 889 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MYH10	NM_001256012.3 linkuse as main transcript	c.5706+4C>T	splice_donor_region_variant, intron_variant	ENST00000360416.8	NP_001242941.1
MYH10	NM_001256095.2 linkuse as main transcript	c.5640+4C>T	splice_donor_region_variant, intron_variant		NP_001243024.1
MYH10	NM_001375266.1 linkuse as main transcript	c.5643+4C>T	splice_donor_region_variant, intron_variant		NP_001362195.1
MYH10	NM_005964.5 linkuse as main transcript	c.5613+4C>T	splice_donor_region_variant, intron_variant		NP_005955.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH10	ENST00000360416.8 linkuse as main transcript	c.5706+4C>T		splice_donor_region_variant, intron_variant		1	NM_001256012.3	ENSP00000353590		P35580-4

Frequencies

GnomAD3 genomes

AF:

0.00583

AC:

887

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00361

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00595

AC:

1496

AN:

251276

Hom.:

AF XY:

0.00599

AC XY:

813

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00186

Gnomad FIN exome

AF:

0.00550

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00820

AC:

11987

AN:

1460956

Hom.:

Cov.:

AF XY:

0.00806

AC XY:

5861

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.00631

Gnomad4 NFE exome

AF:

0.00981

Gnomad4 OTH exome

AF:

0.00666

GnomAD4 genome

AF:

0.00584

AC:

889

AN:

152178

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

401

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00360

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00858

Hom.:

Bravo

AF:

0.00529

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00889

EpiControl

AF:

0.00806

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.0

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