Variant 2-219435093-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_005876.5(SPEG):c.116T>C(p.Val39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,461,702 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0087 ( 20 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 12 hom. )

Consequence

SPEG
NM_005876.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -2.17

Variant links:

Genes affected

SPEG (HGNC:16901): (striated muscle enriched protein kinase) This gene encodes a protein with similarity to members of the myosin light chain kinase family. This protein family is required for myocyte cytoskeletal development. Along with the desmin gene, expression of this gene may be controlled by the desmin locus control region. Mutations in this gene are associated with centronuclear myopathy 5. [provided by RefSeq, Jun 2016]

SPEG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002774924).

BP6

Variant 2-219435093-T-C is Benign according to our data. Variant chr2-219435093-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 287260.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00874 (1330/152168) while in subpopulation AFR AF= 0.0302 (1256/41528). AF 95% confidence interval is 0.0289. There are 20 homozygotes in gnomad4. There are 630 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPEG	NM_005876.5 linkuse as main transcript	c.116T>C	p.Val39Ala	missense_variant	1/41	ENST00000312358.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPEG	ENST00000312358.12 linkuse as main transcript	c.116T>C	p.Val39Ala	missense_variant	1/41	5	NM_005876.5	P1	Q15772-5

Frequencies

GnomAD3 genomes

AF:

0.00873

AC:

1328

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0303

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.000551

AC:

AN:

56248

Hom.:

AF XY:

0.000399

AC XY:

AN XY:

32616

show subpopulations

Gnomad AFR exome

AF:

0.0262

Gnomad AMR exome

AF:

0.000768

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:

0.00116

GnomAD4 exome

AF:

0.000677

AC:

886

AN:

1309534

Hom.:

Cov.:

AF XY:

0.000562

AC XY:

362

AN XY:

643714

show subpopulations

Gnomad4 AFR exome

AF:

0.0292

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000288

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000667

Gnomad4 OTH exome

AF:

0.00160

GnomAD4 genome

AF:

0.00874

AC:

1330

AN:

152168

Hom.:

Cov.:

AF XY:

0.00847

AC XY:

630

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0302

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00617

Hom.:

Bravo

AF:

0.00967

ExAC

AF:

0.000680

AC:

Asia WGS

AF:

0.00116

AC:

AN:

3468

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 30, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.10

DANN

Benign

0.54

DEOGEN2

Benign

0.045

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.33

REVEL

Benign

0.048

Sift

Benign

0.96

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.084

MVP

0.48

MPC

0.78

ClinPred

0.0045

GERP RS

-3.4

Varity_R

0.035

gMVP

0.085

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