17-8478334-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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

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]

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]

ACMG classification

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 GnomAd at 887 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH10	NM_001256012.3	c.5706+4C>T		splice_donor_region_variant, intron_variant		ENST00000360416.8
MYH10	NM_001256095.2	c.5640+4C>T		splice_donor_region_variant, intron_variant
MYH10	NM_001375266.1	c.5643+4C>T		splice_donor_region_variant, intron_variant
MYH10	NM_005964.5	c.5613+4C>T		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH10	ENST00000360416.8	c.5706+4C>T		splice_donor_region_variant, intron_variant		1	NM_001256012.3

Frequencies

GnomAD3 genomes AF: 0.00583 AC: 887 AN: 152060 Hom.: 3 Cov.: 32

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.: 9 AF XY: 0.00599 AC XY: 813 AN XY: 135796

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.: 57 Cov.: 31 AF XY: 0.00806 AC XY: 5861 AN XY: 726802

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.: 3 Cov.: 32 AF XY: 0.00539 AC XY: 401 AN XY: 74394

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.: 6

Bravo AF: 0.00529

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00889

EpiControl AF: 0.00806

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

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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

Other links and lift over

dbSNP: rs72841802; hg19: chr17-8381652;