3-108383733-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_014981.3(MYH15):​c.5632-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,028,758 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 29)
Exomes 𝑓: 0.0027 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MYH15
NM_014981.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.240
Variant links:
Genes affected
MYH15 (HGNC:31073): (myosin heavy chain 15) Predicted to enable several functions, including ATP binding activity; actin filament binding activity; and calmodulin binding activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 3-108383733-T-TA is Benign according to our data. Variant chr3-108383733-T-TA is described in ClinVar as [Benign]. Clinvar id is 791941.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00271 (2786/1028758) while in subpopulation AMR AF= 0.0266 (410/15414). AF 95% confidence interval is 0.0245. There are 0 homozygotes in gnomad4_exome. There are 1678 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 2786 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYH15NM_014981.3 linkc.5632-5dupT splice_region_variant, intron_variant Intron 39 of 40 ENST00000693548.1 NP_055796.2 Q9Y2K3
MYH15XM_011512559.3 linkc.5692-5dupT splice_region_variant, intron_variant Intron 41 of 42 XP_011510861.1 Q9Y2K3
LOC124900545XR_007095998.1 linkn.112+2087dupA intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYH15ENST00000693548.1 linkc.5632-5_5632-4insT splice_region_variant, intron_variant Intron 39 of 40 NM_014981.3 ENSP00000508967.1 A0A8I5KXJ3
MYH15ENST00000273353.5 linkc.5632-5_5632-4insT splice_region_variant, intron_variant Intron 40 of 41 1 ENSP00000273353.4 Q9Y2K3
MYH15ENST00000689784.1 linkc.4651-5_4651-4insT splice_region_variant, intron_variant Intron 31 of 32 ENSP00000509841.1 A0A8I5KYE8

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
126
AN:
58940
Hom.:
0
Cov.:
29
FAILED QC
Gnomad AFR
AF:
0.00243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00107
Gnomad ASJ
AF:
0.00175
Gnomad EAS
AF:
0.00711
Gnomad SAS
AF:
0.000805
Gnomad FIN
AF:
0.00195
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00191
Gnomad OTH
AF:
0.00542
GnomAD3 exomes
AF:
0.0233
AC:
1309
AN:
56170
Hom.:
0
AF XY:
0.0227
AC XY:
695
AN XY:
30628
show subpopulations
Gnomad AFR exome
AF:
0.00688
Gnomad AMR exome
AF:
0.0241
Gnomad ASJ exome
AF:
0.0241
Gnomad EAS exome
AF:
0.0377
Gnomad SAS exome
AF:
0.0300
Gnomad FIN exome
AF:
0.0498
Gnomad NFE exome
AF:
0.0222
Gnomad OTH exome
AF:
0.0257
GnomAD4 exome
AF:
0.00271
AC:
2786
AN:
1028758
Hom.:
0
Cov.:
31
AF XY:
0.00333
AC XY:
1678
AN XY:
503402
show subpopulations
Gnomad4 AFR exome
AF:
0.00197
Gnomad4 AMR exome
AF:
0.0266
Gnomad4 ASJ exome
AF:
0.00504
Gnomad4 EAS exome
AF:
0.00435
Gnomad4 SAS exome
AF:
0.0145
Gnomad4 FIN exome
AF:
0.00885
Gnomad4 NFE exome
AF:
0.00148
Gnomad4 OTH exome
AF:
0.00224
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00214
AC:
126
AN:
58992
Hom.:
0
Cov.:
29
AF XY:
0.00226
AC XY:
63
AN XY:
27902
show subpopulations
Gnomad4 AFR
AF:
0.00242
Gnomad4 AMR
AF:
0.00106
Gnomad4 ASJ
AF:
0.00175
Gnomad4 EAS
AF:
0.00714
Gnomad4 SAS
AF:
0.000812
Gnomad4 FIN
AF:
0.00195
Gnomad4 NFE
AF:
0.00191
Gnomad4 OTH
AF:
0.00539

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 11, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs377049870; hg19: chr3-108102580; API