chr17-10411058-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002472.3(MYH8):​c.1417-111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,553,184 control chromosomes in the GnomAD database, including 128,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12118 hom., cov: 32)
Exomes 𝑓: 0.39 ( 116370 hom. )

Consequence

MYH8
NM_002472.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.26

Publications

4 publications found
Variant links:
Genes affected
MYH8 (HGNC:7578): (myosin heavy chain 8) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]
MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BP6
Variant 17-10411058-G-A is Benign according to our data. Variant chr17-10411058-G-A is described in ClinVar as [Benign]. Clinvar id is 1181307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYH8NM_002472.3 linkc.1417-111C>T intron_variant Intron 14 of 39 ENST00000403437.2 NP_002463.2 P13535
MYHASNR_125367.1 linkn.167+4820G>A intron_variant Intron 2 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYH8ENST00000403437.2 linkc.1417-111C>T intron_variant Intron 14 of 39 5 NM_002472.3 ENSP00000384330.2 P13535

Frequencies

GnomAD3 genomes
AF:
0.379
AC:
57577
AN:
151830
Hom.:
12109
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.276
Gnomad AMI
AF:
0.411
Gnomad AMR
AF:
0.460
Gnomad ASJ
AF:
0.397
Gnomad EAS
AF:
0.867
Gnomad SAS
AF:
0.634
Gnomad FIN
AF:
0.436
Gnomad MID
AF:
0.408
Gnomad NFE
AF:
0.359
Gnomad OTH
AF:
0.367
GnomAD4 exome
AF:
0.392
AC:
549394
AN:
1401236
Hom.:
116370
AF XY:
0.398
AC XY:
277141
AN XY:
696248
show subpopulations
African (AFR)
AF:
0.269
AC:
8444
AN:
31406
American (AMR)
AF:
0.563
AC:
22855
AN:
40586
Ashkenazi Jewish (ASJ)
AF:
0.403
AC:
10268
AN:
25472
East Asian (EAS)
AF:
0.847
AC:
31638
AN:
37350
South Asian (SAS)
AF:
0.612
AC:
50414
AN:
82380
European-Finnish (FIN)
AF:
0.424
AC:
20585
AN:
48592
Middle Eastern (MID)
AF:
0.414
AC:
2172
AN:
5250
European-Non Finnish (NFE)
AF:
0.354
AC:
379302
AN:
1072070
Other (OTH)
AF:
0.408
AC:
23716
AN:
58130
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
16255
32511
48766
65022
81277
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
12392
24784
37176
49568
61960
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.379
AC:
57623
AN:
151948
Hom.:
12118
Cov.:
32
AF XY:
0.393
AC XY:
29184
AN XY:
74246
show subpopulations
African (AFR)
AF:
0.276
AC:
11441
AN:
41454
American (AMR)
AF:
0.460
AC:
7015
AN:
15250
Ashkenazi Jewish (ASJ)
AF:
0.397
AC:
1377
AN:
3466
East Asian (EAS)
AF:
0.866
AC:
4476
AN:
5168
South Asian (SAS)
AF:
0.634
AC:
3052
AN:
4816
European-Finnish (FIN)
AF:
0.436
AC:
4599
AN:
10544
Middle Eastern (MID)
AF:
0.411
AC:
120
AN:
292
European-Non Finnish (NFE)
AF:
0.359
AC:
24389
AN:
67936
Other (OTH)
AF:
0.369
AC:
779
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1718
3436
5154
6872
8590
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
572
1144
1716
2288
2860
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.354
Hom.:
1248
Bravo
AF:
0.373
Asia WGS
AF:
0.712
AC:
2472
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Nov 12, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.21
DANN
Benign
0.48
PhyloP100
-2.3
Mutation Taster
=100/0
polymorphism (auto)

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: rs12601552; hg19: chr17-10314375; COSMIC: COSV107504935; API