dbSNP rs555185796: MIER2:p.Asp451Asn (chr19-307384-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017550.3(MIER2):c.1351G>A(p.Asp451Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,606,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

MIER2
NM_017550.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.03

Publications

0 publications found

Variant links:

Genes affected

MIER2 (HGNC:29210): (MIER family member 2) Enables histone deacetylase binding activity. Contributes to histone deacetylase activity. Involved in histone deacetylation. Located in cytoplasm and nucleus. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

MIER2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03820896).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017550.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIER2	NM_017550.3	MANE Select	c.1351G>A	p.Asp451Asn	missense	Exon 13 of 14	NP_060020.1	Q8N344
MIER2	NM_001387152.1		c.1357G>A	p.Asp453Asn	missense	Exon 13 of 14	NP_001374081.1
MIER2	NM_001387153.1		c.1330G>A	p.Asp444Asn	missense	Exon 13 of 14	NP_001374082.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIER2	ENST00000264819.7	TSL:1 MANE Select	c.1351G>A	p.Asp451Asn	missense	Exon 13 of 14	ENSP00000264819.3	Q8N344
MIER2	ENST00000931432.1		c.1258G>A	p.Asp420Asn	missense	Exon 12 of 13	ENSP00000601491.1
MIER2	ENST00000871288.1		c.1225G>A	p.Asp409Asn	missense	Exon 12 of 13	ENSP00000541347.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000300

AC:

AN:

233670

AF XY:

0.0000393

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000284

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.0000268

AC:

AN:

1454772

Hom.:

Cov.:

AF XY:

0.0000318

AC XY:

AN XY:

723026

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

43854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25926

East Asian (EAS)

AF:

0.00

AC:

AN:

39466

South Asian (SAS)

AF:

0.000212

AC:

AN:

84894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1109874

Other (OTH)

AF:

0.0000333

AC:

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000460

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000337

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.65

M_CAP

Benign

0.0052

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.040

REVEL

Benign

0.013

Sift

Benign

0.17

Sift4G

Benign

0.30

Polyphen

0.0020

Vest4

0.057

MVP

0.10

MPC

0.19

ClinPred

0.021

GERP RS

-0.30

Varity_R

0.046

gMVP

0.17

Mutation Taster

=98/2

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over