Genetic Variant NM_017550.3:c.1351G>T (chr19-307384-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017550.3(MIER2):c.1351G>T(p.Asp451Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D451N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MIER2
NM_017550.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118352234).

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>T	p.Asp451Tyr	missense	Exon 13 of 14	NP_060020.1	Q8N344
MIER2	NM_001387152.1		c.1357G>T	p.Asp453Tyr	missense	Exon 13 of 14	NP_001374081.1
MIER2	NM_001387153.1		c.1330G>T	p.Asp444Tyr	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>T	p.Asp451Tyr	missense	Exon 13 of 14	ENSP00000264819.3	Q8N344
MIER2	ENST00000931432.1		c.1258G>T	p.Asp420Tyr	missense	Exon 12 of 13	ENSP00000601491.1
MIER2	ENST00000871288.1		c.1225G>T	p.Asp409Tyr	missense	Exon 12 of 13	ENSP00000541347.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000428

AC:

AN:

233670

AF XY:

0.00000787

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:

0.00000948

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454772

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723026

show subpopulations

African (AFR)

AF:

0.00

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:

0.00

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:

9.01e-7

AC:

AN:

1109874

Other (OTH)

AF:

0.00

AC:

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.5

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.042

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.73

M_CAP

Benign

0.0091

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-1.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.3

REVEL

Benign

0.016

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.022

Polyphen

0.69

Vest4

0.24

MutPred

0.25

Gain of catalytic residue at D451 (P = 0.0109)

MVP

0.043

MPC

0.45

ClinPred

0.095

GERP RS

-0.30

Varity_R

0.083

gMVP

0.40

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over