Variant 5-137870935-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The ENST00000239926.9(MYOT):c.284G>T(p.Ser95Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MYOT
ENST00000239926.9 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.20

Variant links:

Genes affected

MYOT (HGNC:12399): (myotilin) This gene encodes a cystoskeletal protein which plays a significant role in the stability of thin filaments during muscle contraction. This protein binds F-actin, crosslinks actin filaments, and prevents latrunculin A-induced filament disassembly. Mutations in this gene have been associated with limb-girdle muscular dystrophy and myofibrillar myopathies. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.[provided by RefSeq, Oct 2008]

MYOT links:

PKD2L2-DT (HGNC:55557): (PKD2L2 divergent transcript)

PKD2L2-DT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.748

PP5

Variant 5-137870935-G-T is Pathogenic according to our data. Variant chr5-137870935-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 5838.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-137870935-G-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOT	NM_006790.3 linkuse as main transcript	c.284G>T	p.Ser95Ile	missense_variant	2/10	ENST00000239926.9	NP_006781.1
PKD2L2-DT	XR_948815.3 linkuse as main transcript	n.303-11672C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOT	ENST00000239926.9 linkuse as main transcript	c.284G>T	p.Ser95Ile	missense_variant	2/10	1	NM_006790.3	ENSP00000239926	P1
PKD2L2-DT	ENST00000514616.6 linkuse as main transcript	n.320-11672C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Myofibrillar myopathy 3

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 27, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.016

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.84

M_CAP

Benign

0.052

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.78

MutationTaster

Benign

0.088

A;A;A

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.35

Sift

Uncertain

0.0070

Sift4G

Benign

0.23

Vest4

0.71

MutPred

0.42

Loss of glycosylation at S99 (P = 0.0617);

MVP

0.85

MPC

0.27

ClinPred

0.53

GERP RS

4.1

gMVP

0.60

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.

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