Genetic Variant MIER3:n.*2762A>G (chr5-56921702-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000452157.5(MIER3):n.*2762A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 152,690 control chromosomes in the GnomAD database, including 656 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.091 ( 655 hom., cov: 33)

Exomes 𝑓: 0.099 ( 1 hom. )

Consequence

MIER3
ENST00000452157.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.826

Publications

10 publications found

Variant links:

Genes affected

MIER3 (HGNC:26678): (MIER family member 3) Predicted to enable histone deacetylase binding activity and transcription corepressor activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

MIER3 links:

SETD9 (HGNC:28508): (SET domain containing 9) Predicted to enable lysine N-methyltransferase activity. Predicted to be involved in regulation of signal transduction by p53 class mediator. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SETD9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIER3	NM_001297599.2 link	c.*1426A>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000381199.8	NP_001284528.1	Q7Z3K6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIER3	ENST00000381199.8 link	c.*1426A>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_001297599.2	ENSP00000370596.3		Q7Z3K6-1

Frequencies

GnomAD3 genomes

AF:

0.0910

AC:

13846

AN:

152138

Hom.:

655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0840

Gnomad ASJ

AF:

0.0960

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0827

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0914

Gnomad OTH

AF:

0.0991

GnomAD4 exome

AF:

0.0991

AC:

AN:

434

Hom.:

Cov.:

AF XY:

0.0885

AC XY:

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0967

AC:

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0910

AC:

13862

AN:

152256

Hom.:

655

Cov.:

AF XY:

0.0918

AC XY:

6837

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0876

AC:

3641

AN:

41562

American (AMR)

AF:

0.0838

AC:

1283

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0960

AC:

333

AN:

3468

East Asian (EAS)

AF:

0.142

AC:

736

AN:

5186

South Asian (SAS)

AF:

0.102

AC:

490

AN:

4822

European-Finnish (FIN)

AF:

0.0827

AC:

877

AN:

10602

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0915

AC:

6219

AN:

67998

Other (OTH)

AF:

0.0981

AC:

207

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

669

1338

2007

2676

3345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0937

Hom.:

1077

Bravo

AF:

0.0922

Asia WGS

AF:

0.104

AC:

362

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over