22-36282079-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002473.6(MYH9):​c.*589G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000059 in 237,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

MYH9
NM_002473.6 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.71

Publications

1 publications found
Variant links:
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]
MYH9 Gene-Disease associations (from GenCC):
  • autosomal dominant nonsyndromic hearing loss 17
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
  • May-Hegglin anomaly
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • autosomal dominant nonsyndromic hearing loss
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BS1
Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000118 (10/85022) while in subpopulation NFE AF = 0.000193 (10/51892). AF 95% confidence interval is 0.000104. There are 0 homozygotes in GnomAdExome4. There are 6 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.
BS2
High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYH9NM_002473.6 linkc.*589G>C 3_prime_UTR_variant Exon 41 of 41 ENST00000216181.11 NP_002464.1 P35579-1A0A024R1N1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYH9ENST00000216181.11 linkc.*589G>C 3_prime_UTR_variant Exon 41 of 41 1 NM_002473.6 ENSP00000216181.6 P35579-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152222
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000118
AC:
10
AN:
85022
Hom.:
0
Cov.:
0
AF XY:
0.000152
AC XY:
6
AN XY:
39404
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
3826
American (AMR)
AF:
0.00
AC:
0
AN:
3770
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
5050
East Asian (EAS)
AF:
0.00
AC:
0
AN:
11418
South Asian (SAS)
AF:
0.00
AC:
0
AN:
1236
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
506
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
488
European-Non Finnish (NFE)
AF:
0.000193
AC:
10
AN:
51892
Other (OTH)
AF:
0.00
AC:
0
AN:
6836
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.435
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152222
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74368
show subpopulations
African (AFR)
AF:
0.0000482
AC:
2
AN:
41460
American (AMR)
AF:
0.00
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10632
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68036
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.438
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.054
DANN
Benign
0.40
PhyloP100
-2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1

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

Other links and lift over

dbSNP: rs116572976; hg19: chr22-36678125; API