chr17-8475843-G-A

Variant names:

• chr17-8475843-G-A
• rs77306726
• NM_001256012.3:c.5985C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001256012.3(MYH10):​c.5985C>T​(p.Thr1995Thr) variant causes a synonymous change. The variant allele was found at a frequency of 0.000408 in 1,614,180 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (3 hom.)
• Consequence: MYH10 NM_001256012.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.17
• Publications: 0 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]

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 17-8475843-G-A is Benign according to our data. Variant chr17-8475843-G-A is described in ClinVar as Benign. ClinVar VariationId is 712206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 344 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH10	NM_001256012.3	MANE Select	c.5985C>T	p.Thr1995Thr	synonymous	Exon 43 of 43	NP_001242941.1	P35580-4
	MYH10	NM_001375266.1		c.5922C>T	p.Thr1974Thr	synonymous	Exon 42 of 42	NP_001362195.1	A0A8I5KZ38
	MYH10	NM_001256095.2		c.5919C>T	p.Thr1973Thr	synonymous	Exon 42 of 42	NP_001243024.1	P35580-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH10	ENST00000360416.8	TSL:1 MANE Select	c.5985C>T	p.Thr1995Thr	synonymous	Exon 43 of 43	ENSP00000353590.4	P35580-4
	MYH10	ENST00000379980.8	TSL:1	c.5919C>T	p.Thr1973Thr	synonymous	Exon 42 of 42	ENSP00000369315.5	P35580-5
	MYH10	ENST00000269243.8	TSL:1	c.5892C>T	p.Thr1964Thr	synonymous	Exon 41 of 41	ENSP00000269243.4	P35580-1

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 337 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00773

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000597 AC: 150 AN: 251446 AF XY: 0.000442

Gnomad AFR exome AF: 0.00837

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000215 AC: 314 AN: 1461884 Hom.: 3 Cov.: 31 AF XY: 0.000228 AC XY: 166 AN XY: 727242

African (AFR) AF: 0.00762 AC: 255 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112008

Other (OTH) AF: 0.000563 AC: 34 AN: 60396

GnomAD4 genome AF: 0.00226 AC: 344 AN: 152296 Hom.: 1 Cov.: 33 AF XY: 0.00224 AC XY: 167 AN XY: 74470

African (AFR) AF: 0.00787 AC: 327 AN: 41542

American (AMR) AF: 0.000588 AC: 9 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00115 Hom.: 1

Bravo AF: 0.00247

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	MYH10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.0
DANN	Benign	0.91
PhyloP100		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs77306726; hg19: chr17-8379161;