NM_002473.6:c.3100+632C>T

Variant names:

• chr22-36298287-G-A
• rs739101
• NM_002473.6:c.3100+632C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002473.6(MYH9):​c.3100+632C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,800 control chromosomes in the GnomAD database, including 24,070 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 0.53 (24070 hom., cov: 30)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 3 publications found

Genes affected

MYH9 (HGNC:7579): (myosin heavy chain 9) This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness. [provided by RefSeq, Dec 2011]

MYH9 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 17

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• May-Hegglin anomaly

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002473.6. 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
	MYH9	NM_002473.6	MANE Select	c.3100+632C>T		intron	N/A	NP_002464.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	ENST00000216181.11	TSL:1 MANE Select	c.3100+632C>T		intron	N/A	ENSP00000216181.6
	MYH9	ENST00000685801.1		c.3163+632C>T		intron	N/A	ENSP00000510688.1
	MYH9	ENST00000691109.1		n.3395+632C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79738 AN: 151682 Hom.: 24075 Cov.: 30

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.525 AC: 79737 AN: 151800 Hom.: 24070 Cov.: 30 AF XY: 0.521 AC XY: 38657 AN XY: 74192

African (AFR) AF: 0.240 AC: 9933 AN: 41380

American (AMR) AF: 0.613 AC: 9343 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1807 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1153 AN: 5154

South Asian (SAS) AF: 0.381 AC: 1828 AN: 4804

European-Finnish (FIN) AF: 0.659 AC: 6954 AN: 10554

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46697 AN: 67884

Other (OTH) AF: 0.538 AC: 1137 AN: 2112

Alfa AF: 0.541 Hom.: 3597

Bravo AF: 0.511

Asia WGS AF: 0.253 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.84
PhyloP100		0.068
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: rs739101; hg19: chr22-36694333;