rs16996704

Variant names:

• chr22-36368743-A-G
• rs16996704
• NM_002473.6:c.-20+19064T>C

Variant summary

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

The NM_002473.6(MYH9):​c.-20+19064T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,918 control chromosomes in the GnomAD database, including 4,916 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 0.22 (4916 hom., cov: 31)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.-20+19064T>C		intron_variant	Intron 1 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.-20+19064T>C		intron_variant	Intron 1 of 40	1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33065 AN: 151800 Hom.: 4897 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.218 AC: 33137 AN: 151918 Hom.: 4916 Cov.: 31 AF XY: 0.217 AC XY: 16106 AN XY: 74290

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.187

Alfa AF: 0.146 Hom.: 1151

Bravo AF: 0.229

Asia WGS AF: 0.157 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.7
DANN	Benign	0.79

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: rs16996704; hg19: chr22-36764788;