rs9610486

Variant names:

• chr22-36297396-G-A
• rs9610486
• NM_002473.6:c.3101-382C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36297396-G-A
• chr22-36297396-G-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.3101-382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 207,536 control chromosomes in the GnomAD database, including 34,427 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 (24116 hom., cov: 33)
  • Exomes 𝑓: 0.58 (10311 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.3101-382C>T		intron_variant	Intron 24 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.3101-382C>T		intron_variant	Intron 24 of 40	1	NM_002473.6	ENSP00000216181.6
MYH9	ENST00000685801.1	c.3164-382C>T		intron_variant	Intron 25 of 41			ENSP00000510688.1
MYH9	ENST00000691109.1	n.3396-382C>T		intron_variant	Intron 18 of 34
MYH9	ENST00000459960.1	n.-73C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79907 AN: 151976 Hom.: 24121 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.583 AC: 32302 AN: 55442 Hom.: 10311 AF XY: 0.561 AC XY: 16934 AN XY: 30166

African (AFR) AF: 0.200 AC: 283 AN: 1412

American (AMR) AF: 0.608 AC: 1489 AN: 2448

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 830 AN: 1614

East Asian (EAS) AF: 0.201 AC: 399 AN: 1982

South Asian (SAS) AF: 0.375 AC: 3568 AN: 9508

European-Finnish (FIN) AF: 0.657 AC: 1851 AN: 2816

Middle Eastern (MID) AF: 0.519 AC: 111 AN: 214

European-Non Finnish (NFE) AF: 0.678 AC: 22054 AN: 32514

Other (OTH) AF: 0.585 AC: 1717 AN: 2934

GnomAD4 genome AF: 0.525 AC: 79906 AN: 152094 Hom.: 24116 Cov.: 33 AF XY: 0.521 AC XY: 38731 AN XY: 74356

African (AFR) AF: 0.240 AC: 9968 AN: 41454

American (AMR) AF: 0.613 AC: 9365 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1808 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1165 AN: 5178

South Asian (SAS) AF: 0.381 AC: 1837 AN: 4822

European-Finnish (FIN) AF: 0.656 AC: 6943 AN: 10580

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.688 AC: 46801 AN: 68004

Other (OTH) AF: 0.539 AC: 1139 AN: 2114

Alfa AF: 0.632 Hom.: 15315

Bravo AF: 0.511

Asia WGS AF: 0.253 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.76
DANN	Benign	0.76
PhyloP100		-0.19
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: rs9610486; hg19: chr22-36693442;