rs371688

Variant names:

• chr17-8594767-C-A
• rs371688
• NM_001256012.3:c.503-5659G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256012.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH10	NM_001256012.3	MANE Select	c.503-5659G>T		intron	N/A	NP_001242941.1
	MYH10	NM_001375266.1		c.503-5659G>T		intron	N/A	NP_001362195.1
	MYH10	NM_001256095.2		c.503-5659G>T		intron	N/A	NP_001243024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH10	ENST00000360416.8	TSL:1 MANE Select	c.503-5659G>T		intron	N/A	ENSP00000353590.4
	MYH10	ENST00000379980.8	TSL:1	c.503-5659G>T		intron	N/A	ENSP00000369315.5
	MYH10	ENST00000269243.8	TSL:1	c.503-5659G>T		intron	N/A	ENSP00000269243.4

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

African (AFR) AF: 0.922 AC: 38284 AN: 41510

American (AMR) AF: 0.990 AC: 15142 AN: 15298

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5180

South Asian (SAS) AF: 1.00 AC: 4832 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68026 AN: 68038

Other (OTH) AF: 0.986 AC: 2085 AN: 2114

Alfa AF: 0.984 Hom.: 9519

Bravo AF: 0.974

Asia WGS AF: 0.997 AC: 3468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.29
DANN	Benign	0.26
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs371688; hg19: chr17-8498085;