Variant 3-108383733-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_014981.3(MYH15):c.5632-4A>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00077 in 1,033,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 17)

Exomes 𝑓: 0.00077 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

MYH15
NM_014981.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00007305

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.369

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]

MYH15 links:

LOC124900545 (HGNC:):

LOC124900545 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 3-108383733-T-A is Benign according to our data. Variant chr3-108383733-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 711388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAdExome4 at 796 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MYH15	NM_014981.3 linkuse as main transcript	c.5632-4A>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000693548.1	NP_055796.2
LOC124900545	XR_007095998.1 linkuse as main transcript	n.112+2082T>A	intron_variant, non_coding_transcript_variant
MYH15	XM_011512559.3 linkuse as main transcript	c.5692-4A>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_011510861.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
MYH15	ENST00000693548.1 linkuse as main transcript	c.5632-4A>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NM_014981.3	ENSP00000508967	P1
MYH15	ENST00000273353.5 linkuse as main transcript	c.5632-4A>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000273353	P1
MYH15	ENST00000689784.1 linkuse as main transcript	c.4651-4A>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			ENSP00000509841

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

59174

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000607

Gnomad AMI

AF:

0.00301

Gnomad AMR

AF:

0.00107

Gnomad ASJ

AF:

0.00172

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00320

Gnomad FIN

AF:

0.00665

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.00135

GnomAD3 exomes

AF:

0.00208

AC:

117

AN:

56170

Hom.:

AF XY:

0.00232

AC XY:

AN XY:

30628

show subpopulations

Gnomad AFR exome

AF:

0.000459

Gnomad AMR exome

AF:

0.00251

Gnomad ASJ exome

AF:

0.00115

Gnomad EAS exome

AF:

0.00410

Gnomad SAS exome

AF:

0.00290

Gnomad FIN exome

AF:

0.00498

Gnomad NFE exome

AF:

0.00194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000770

AC:

796

AN:

1033904

Hom.:

Cov.:

AF XY:

0.000912

AC XY:

462

AN XY:

506446

show subpopulations

Gnomad4 AFR exome

AF:

0.000472

Gnomad4 AMR exome

AF:

0.00397

Gnomad4 ASJ exome

AF:

0.00216

Gnomad4 EAS exome

AF:

0.00111

Gnomad4 SAS exome

AF:

0.00378

Gnomad4 FIN exome

AF:

0.00214

Gnomad4 NFE exome

AF:

0.000497

Gnomad4 OTH exome

AF:

0.000759

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00165

AC:

AN:

59226

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

AN XY:

27972

show subpopulations

Gnomad4 AFR

AF:

0.000605

Gnomad4 AMR

AF:

0.00106

Gnomad4 ASJ

AF:

0.00172

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00323

Gnomad4 FIN

AF:

0.00665

Gnomad4 NFE

AF:

0.00223

Gnomad4 OTH

AF:

0.00134

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 25, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000073

dbscSNV1_RF

Benign

0.044

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over