Variant rs3900940 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014981.3(MYH15):c.3313A>T(p.Thr1105Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MYH15
NM_014981.3 missense, splice_region

Scores

Splicing: ADA: 0.0008983

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09736058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH15	NM_014981.3 linkuse as main transcript	c.3313A>T	p.Thr1105Ser	missense_variant, splice_region_variant	27/41	ENST00000693548.1	NP_055796.2
MYH15	XM_011512559.3 linkuse as main transcript	c.3373A>T	p.Thr1125Ser	missense_variant, splice_region_variant	29/43		XP_011510861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYH15	ENST00000693548.1 linkuse as main transcript	c.3313A>T	p.Thr1105Ser	missense_variant, splice_region_variant	27/41		NM_014981.3	ENSP00000508967	P1
MYH15	ENST00000273353.5 linkuse as main transcript	c.3313A>T	p.Thr1105Ser	missense_variant, splice_region_variant	28/42	1		ENSP00000273353	P1
MYH15	ENST00000689784.1 linkuse as main transcript	c.2332A>T	p.Thr778Ser	missense_variant, splice_region_variant	19/33			ENSP00000509841
MYH15	ENST00000478998.5 linkuse as main transcript	n.1365A>T		splice_region_variant, non_coding_transcript_exon_variant	10/16	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000428

AC:

AN:

233408

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000332

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716850

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000254

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.5

DANN

Benign

0.95

DEOGEN2

Benign

0.042

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.67

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.70

M_CAP

Benign

0.042

MetaRNN

Benign

0.097

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.99

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.19

REVEL

Benign

0.14

Sift

Uncertain

0.015

Sift4G

Benign

0.23

Polyphen

0.28

Vest4

0.048

MutPred

0.25

Loss of ubiquitination at K1128 (P = 0.0787);

MVP

0.62

MPC

0.075

ClinPred

0.12

GERP RS

-1.7

Varity_R

0.038

gMVP

0.040

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00090

dbscSNV1_RF

Benign

0.098

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over