rs371688

Positions:

• chr17-8594767-C-A
• chr17-8594767-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256012.3(MYH10):​c.503-5659G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.978 in 152,278 control chromosomes in the GnomAD database, including 72,856 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 0.98 (72856 hom., cov: 33)
• Consequence: MYH10 NM_001256012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH10	NM_001256012.3	c.503-5659G>T		intron_variant		ENST00000360416.8	NP_001242941.1
MYH10	NM_001375266.1	c.503-5659G>T		intron_variant			NP_001362195.1
MYH10	NM_001256095.2	c.503-5659G>T		intron_variant			NP_001243024.1
MYH10	NM_005964.5	c.503-5659G>T		intron_variant			NP_005955.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH10	ENST00000360416.8	c.503-5659G>T		intron_variant		1	NM_001256012.3	ENSP00000353590.4

Frequencies

GnomAD3 genomes AF: 0.978 AC: 148739 AN: 152160 Hom.: 72799 Cov.: 33

Gnomad AFR AF: 0.922

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.986

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

GnomAD4 genome AF: 0.978 AC: 148855 AN: 152278 Hom.: 72856 Cov.: 33 AF XY: 0.978 AC XY: 72849 AN XY: 74468

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.990

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.986

Alfa AF: 0.986 Hom.: 9190

Bravo AF: 0.974

Asia WGS AF: 0.997 AC: 3468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.29
DANN	Benign	0.26

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

Other links and lift over

dbSNP: rs371688; hg19: chr17-8498085;