Genetic Variant NM_001297599.2:c.596-63G>A (chr5-56933461-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001297599.2(MIER3):c.596-63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 1,428,914 control chromosomes in the GnomAD database, including 265,900 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 0.50 ( 21466 hom., cov: 33)

Exomes 𝑓: 0.61 ( 244434 hom. )

Consequence

MIER3
NM_001297599.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.563

Publications

13 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297599.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MIER3	NM_001297599.2	MANE Select	c.596-63G>A	intron	N/A	NP_001284528.1	Q7Z3K6-1
MIER3	NM_001297598.2		c.611-63G>A	intron	N/A	NP_001284527.1	Q7Z3K6-2
MIER3	NM_152622.5		c.596-63G>A	intron	N/A	NP_689835.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MIER3	ENST00000381199.8	TSL:1 MANE Select	c.596-63G>A	intron	N/A	ENSP00000370596.3	Q7Z3K6-1
MIER3	ENST00000381226.7	TSL:1	c.611-63G>A	intron	N/A	ENSP00000370624.3	Q7Z3K6-2
MIER3	ENST00000381213.7	TSL:1	c.596-63G>A	intron	N/A	ENSP00000370611.3	Q7Z3K6-3

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76549

AN:

152030

Hom.:

21464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.593

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.660

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.649

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.645

Gnomad OTH

AF:

0.536

GnomAD4 exome

AF:

0.608

AC:

775881

AN:

1276766

Hom.:

244434

AF XY:

0.605

AC XY:

382119

AN XY:

632000

show subpopulations

African (AFR)

AF:

0.296

AC:

8013

AN:

27044

American (AMR)

AF:

0.346

AC:

9566

AN:

27662

Ashkenazi Jewish (ASJ)

AF:

0.666

AC:

13519

AN:

20298

East Asian (EAS)

AF:

0.117

AC:

4005

AN:

34210

South Asian (SAS)

AF:

0.447

AC:

28291

AN:

63222

European-Finnish (FIN)

AF:

0.650

AC:

31465

AN:

48390

Middle Eastern (MID)

AF:

0.617

AC:

3155

AN:

5114

European-Non Finnish (NFE)

AF:

0.649

AC:

647864

AN:

998420

Other (OTH)

AF:

0.573

AC:

30003

AN:

52406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13637

27274

40911

54548

68185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17208

34416

51624

68832

86040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.503

AC:

76579

AN:

152148

Hom.:

21466

Cov.:

AF XY:

0.497

AC XY:

36978

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.303

AC:

12580

AN:

41522

American (AMR)

AF:

0.431

AC:

6585

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.660

AC:

2292

AN:

3472

East Asian (EAS)

AF:

0.110

AC:

571

AN:

5188

South Asian (SAS)

AF:

0.425

AC:

2048

AN:

4824

European-Finnish (FIN)

AF:

0.649

AC:

6860

AN:

10568

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.645

AC:

43812

AN:

67970

Other (OTH)

AF:

0.532

AC:

1123

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1747

3494

5242

6989

8736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<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:

0.590

Hom.:

20166

Bravo

AF:

0.477

Asia WGS

AF:

0.298

AC:

1037

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

(source)

DANN

Benign

0.64

PhyloP100

0.56

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over