17-8476920-G-T

Variant names:

• chr17-8476920-G-T
• rs559417728
• NM_001256012.3:c.5835C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001256012.3(MYH10):​c.5835C>A​(p.Asn1945Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,688 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYH10 NM_001256012.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH10	NM_001256012.3	c.5835C>A	p.Asn1945Lys	missense_variant	Exon 42 of 43	ENST00000360416.8	NP_001242941.1
MYH10	NM_001375266.1	c.5772C>A	p.Asn1924Lys	missense_variant	Exon 41 of 42		NP_001362195.1
MYH10	NM_001256095.2	c.5769C>A	p.Asn1923Lys	missense_variant	Exon 41 of 42		NP_001243024.1
MYH10	NM_005964.5	c.5742C>A	p.Asn1914Lys	missense_variant	Exon 40 of 41		NP_005955.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH10	ENST00000360416.8	c.5835C>A	p.Asn1945Lys	missense_variant	Exon 42 of 43	1	NM_001256012.3	ENSP00000353590.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460688 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Uncertain	0.58	.;.;D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.3	N;.;D
REVEL	Uncertain	0.31
Sift	Benign	0.37	T;.;T
Sift4G	Benign	0.80	T;T;T
Polyphen		0.0010	.;.;B
Vest4		0.65
MutPred		0.41		.;.;Gain of ubiquitination at N1914 (P = 0.0075);
MVP		0.61
MPC		0.46
ClinPred		0.59	D
GERP RS		-3.7
Varity_R		0.42
gMVP		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: rs559417728; hg19: chr17-8380238;