rs1005570

Positions:

• chr22-36319229-A-G
• chr22-36319229-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.1108+311T>C		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.1108+311T>C		intron_variant		1	NM_002473.6	P1

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

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.843

Alfa AF: 0.893 Hom.: 78763

Bravo AF: 0.802

Asia WGS AF: 0.885 AC: 3076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.024
DANN	Benign	0.26

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: rs1005570; hg19: chr22-36715274;