Variant 14-73721461-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001367710.1(MIDEAS):c.2773A>G(p.Ser925Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,614,058 control chromosomes in the GnomAD database, including 1,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.071 ( 924 hom., cov: 32)

Exomes 𝑓: 0.019 ( 1049 hom. )

Consequence

MIDEAS
NM_001367710.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.150

Variant links:

Genes affected

MIDEAS (HGNC:19853): (mitotic deacetylase associated SANT domain protein) Predicted to enable transcription corepressor activity. Predicted to be involved in histone deacetylation; negative regulation of transcription, DNA-templated; and regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MIDEAS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.316504E-4).

BP6

Variant 14-73721461-T-C is Benign according to our data. Variant chr14-73721461-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3126374.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIDEAS	NM_001367710.1 linkuse as main transcript	c.2773A>G	p.Ser925Gly	missense_variant	11/13	ENST00000423556.7	NP_001354639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIDEAS	ENST00000423556.7 linkuse as main transcript	c.2773A>G	p.Ser925Gly	missense_variant	11/13	2	NM_001367710.1	ENSP00000407767	P1

Frequencies

GnomAD3 genomes

AF:

0.0707

AC:

10745

AN:

152070

Hom.:

922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0583

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0159

Gnomad OTH

AF:

0.0627

GnomAD3 exomes

AF:

0.0292

AC:

7269

AN:

249030

Hom.:

430

AF XY:

0.0267

AC XY:

3596

AN XY:

134810

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.0323

Gnomad ASJ exome

AF:

0.0197

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.0307

GnomAD4 exome

AF:

0.0192

AC:

28049

AN:

1461870

Hom.:

1049

Cov.:

AF XY:

0.0189

AC XY:

13744

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.0338

Gnomad4 ASJ exome

AF:

0.0192

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0172

Gnomad4 FIN exome

AF:

0.00331

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.0299

GnomAD4 genome

AF:

0.0707

AC:

10759

AN:

152188

Hom.:

924

Cov.:

AF XY:

0.0688

AC XY:

5119

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.0582

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0184

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.0159

Gnomad4 OTH

AF:

0.0620

Alfa

AF:

0.0175

Hom.:

Bravo

AF:

0.0815

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.204

AC:

898

ESP6500EA

AF:

0.0159

AC:

137

ExAC

AF:

0.0317

AC:

3845

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0229

EpiControl

AF:

0.0211

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;T;.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.57

.;T;T;T

MetaRNN

Benign

0.00093

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

N;N;.;.

MutationTaster

Benign

0.99

P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.37

T;T;T;.

Polyphen

0.0

B;B;.;.

Vest4

0.047

MPC

0.35

ClinPred

0.0036

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.22

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