rs9610486

Positions:

• chr22-36297396-G-A
• chr22-36297396-G-T

Variant summary

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

The ENST00000216181.11(MYH9):​c.3101-382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 207,536 control chromosomes in the GnomAD database, including 34,427 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 0.53 (24116 hom., cov: 33)
  • Exomes 𝑓: 0.58 (10311 hom.)
• Consequence: MYH9 ENST00000216181.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6	c.3101-382C>T		intron_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.3101-382C>T		intron_variant		1	NM_002473.6	ENSP00000216181	P1
MYH9	ENST00000685801.1	c.3164-382C>T		intron_variant				ENSP00000510688
MYH9	ENST00000691109.1	n.3396-382C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79907 AN: 151976 Hom.: 24121 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.583 AC: 32302 AN: 55442 Hom.: 10311 AF XY: 0.561 AC XY: 16934 AN XY: 30166

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.608

Gnomad4 ASJ exome AF: 0.514

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.678

Gnomad4 OTH exome AF: 0.585

GnomAD4 genome AF: 0.525 AC: 79906 AN: 152094 Hom.: 24116 Cov.: 33 AF XY: 0.521 AC XY: 38731 AN XY: 74356

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.539

Alfa AF: 0.618 Hom.: 6948

Bravo AF: 0.511

Asia WGS AF: 0.253 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.76
DANN	Benign	0.76

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: rs9610486; hg19: chr22-36693442;