rs5995281

chr22-36319792-G-Achr22-36319792-G-Cchr22-36319792-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002473.6(MYH9):c.1013-157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0094 in 767,930 control chromosomes in the GnomAD database, including 351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (240 hom., cov: 31)
  • Exomes 𝑓: 0.0041 (111 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-36319792-G-A is Benign according to our data. Variant chr22-36319792-G-A is described in ClinVar as [Benign]. Clinvar id is 1233229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.1013-157C>T		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.1013-157C>T		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4685 AN: 148222 Hom.: 238 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.0000975

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000314

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.00406 AC: 2516 AN: 619590 Hom.: 111 Cov.: 7 AF XY: 0.00319 AC XY: 1053 AN XY: 329862

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.00659

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000124

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000232

Gnomad4 OTH exome AF: 0.00931

GnomAD4 genome AF: 0.0317 AC: 4703 AN: 148340 Hom.: 240 Cov.: 31 AF XY: 0.0307 AC XY: 2217 AN XY: 72312

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.00981

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000975

Gnomad4 NFE AF: 0.000314

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.00769 Hom.: 1

Bravo AF: 0.0346

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.26
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs5995281; hg19: chr22-36715837;