NM_002473.6:c.1108+311T>C

Variant names:

• chr22-36319229-A-G
• rs1005570
• NM_002473.6:c.1108+311T>C

Variant summary

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

The NM_002473.6(MYH9):​c.1108+311T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,074 control chromosomes in the GnomAD database, including 51,949 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 0.81 (51949 hom., cov: 31)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 20 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: Labcorp Genetics (formerly Invitae), G2P
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.911 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	NM_002473.6	MANE Select	c.1108+311T>C		intron	N/A	NP_002464.1	P35579-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	ENST00000216181.11	TSL:1 MANE Select	c.1108+311T>C		intron	N/A	ENSP00000216181.6	P35579-1
	MYH9	ENST00000685801.1		c.1108+311T>C		intron	N/A	ENSP00000510688.1	A0A8I5KWT8
	MYH9	ENST00000955568.1		c.1108+311T>C		intron	N/A	ENSP00000625627.1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123434 AN: 151956 Hom.: 51919 Cov.: 31

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.812 AC: 123519 AN: 152074 Hom.: 51949 Cov.: 31 AF XY: 0.815 AC XY: 60580 AN XY: 74374

African (AFR) AF: 0.567 AC: 23487 AN: 41418

American (AMR) AF: 0.893 AC: 13655 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3113 AN: 3472

East Asian (EAS) AF: 0.913 AC: 4719 AN: 5168

South Asian (SAS) AF: 0.933 AC: 4503 AN: 4824

European-Finnish (FIN) AF: 0.892 AC: 9446 AN: 10586

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61670 AN: 68004

Other (OTH) AF: 0.843 AC: 1778 AN: 2108

Alfa AF: 0.873 Hom.: 174661

Bravo AF: 0.802

Asia WGS AF: 0.885 AC: 3076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.024
DANN	Benign	0.26
PhyloP100		-1.7
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: rs1005570; hg19: chr22-36715274;