22-36376708-G-T

Position:

• chr22-36376708-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002473.6(MYH9):​c.-20+11099C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 152,280 control chromosomes in the GnomAD database, including 424 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 0.045 (424 hom., cov: 31)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6	c.-20+11099C>A		intron_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.-20+11099C>A		intron_variant		1	NM_002473.6	ENSP00000216181	P1

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6871 AN: 152162 Hom.: 421 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.00372

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00401

Gnomad OTH AF: 0.0345

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

GnomAD4 genome AF: 0.0453 AC: 6896 AN: 152280 Hom.: 424 Cov.: 31 AF XY: 0.0455 AC XY: 3392 AN XY: 74480

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00401

Gnomad4 OTH AF: 0.0342

Alfa AF: 0.0185 Hom.: 39

Bravo AF: 0.0558

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.70

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: rs10483194; hg19: chr22-36772753;