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

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_014981.3(MYH15):c.5632-4A>G 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 0.0209 in 1,094,500 control chromosomes in the GnomAD database, including 2,731 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 Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 1474 hom., cov: 17)

Exomes 𝑓: 0.011 ( 1257 hom. )

Consequence

MYH15
NM_014981.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001012

Clinical Significance

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 3-108383733-T-C is Benign according to our data. Variant chr3-108383733-T-C is described in ClinVar as [Benign]. Clinvar id is 767922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MYH15	NM_014981.3 linkuse as main transcript	c.5632-4A>G	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>C	intron_variant, non_coding_transcript_variant
MYH15	XM_011512559.3 linkuse as main transcript	c.5692-4A>G	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>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NM_014981.3	ENSP00000508967	P1
MYH15	ENST00000273353.5 linkuse as main transcript	c.5632-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000273353	P1
MYH15	ENST00000689784.1 linkuse as main transcript	c.4651-4A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			ENSP00000509841

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

11400

AN:

59466

Hom.:

1461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0897

Gnomad ASJ

AF:

0.0325

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0119

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0938

Gnomad NFE

AF:

0.00405

Gnomad OTH

AF:

0.168

GnomAD3 exomes

AF:

0.0824

AC:

4630

AN:

56170

Hom.:

607

AF XY:

0.0613

AC XY:

1878

AN XY:

30628

show subpopulations

Gnomad AFR exome

AF:

0.447

Gnomad AMR exome

AF:

0.0783

Gnomad ASJ exome

AF:

0.0550

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00787

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00459

Gnomad OTH exome

AF:

0.0561

GnomAD4 exome

AF:

0.0111

AC:

11479

AN:

1034982

Hom.:

1257

Cov.:

AF XY:

0.00992

AC XY:

5032

AN XY:

507056

show subpopulations

Gnomad4 AFR exome

AF:

0.321

Gnomad4 AMR exome

AF:

0.0379

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.0000370

Gnomad4 SAS exome

AF:

0.00351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.0270

GnomAD4 genome

AF:

0.192

AC:

11448

AN:

59518

Hom.:

1474

Cov.:

AF XY:

0.192

AC XY:

5394

AN XY:

28110

show subpopulations

Gnomad4 AFR

AF:

0.463

Gnomad4 AMR

AF:

0.0896

Gnomad4 ASJ

AF:

0.0325

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00405

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.0859

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.056

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