rs12159211

chr22-36323118-G-A

Variant summary

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

The NM_002473.6(MYH9):c.613-597C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 152,282 control chromosomes in the GnomAD database, including 165 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 0.042 (165 hom., cov: 33)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.613-597C>T		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.613-597C>T		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6399 AN: 152164 Hom.: 166 Cov.: 33

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.0691

Gnomad EAS AF: 0.0144

Gnomad SAS AF: 0.0602

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0420 AC: 6396 AN: 152282 Hom.: 165 Cov.: 33 AF XY: 0.0418 AC XY: 3110 AN XY: 74462

Gnomad4 AFR AF: 0.0277

Gnomad4 AMR AF: 0.0341

Gnomad4 ASJ AF: 0.0691

Gnomad4 EAS AF: 0.0145

Gnomad4 SAS AF: 0.0596

Gnomad4 FIN AF: 0.0650

Gnomad4 NFE AF: 0.0484

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0437 Hom.: 30

Bravo AF: 0.0393

Asia WGS AF: 0.0430 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.057
Dann	Benign	0.68

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: rs12159211; hg19: chr22-36719163;