Variant 5-56923381-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001297599.2(MIER3):c.1400C>G(p.Pro467Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MIER3
NM_001297599.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13473573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIER3	NM_001297599.2 linkuse as main transcript	c.1400C>G	p.Pro467Arg	missense_variant	13/13	ENST00000381199.8	NP_001284528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIER3	ENST00000381199.8 linkuse as main transcript	c.1400C>G	p.Pro467Arg	missense_variant	13/13	1	NM_001297599.2	ENSP00000370596	A1	Q7Z3K6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.1397C>G (p.P466R) alteration is located in exon 13 (coding exon 13) of the MIER3 gene. This alteration results from a C to G substitution at nucleotide position 1397, causing the proline (P) at amino acid position 466 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;.;T;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.69

.;.;N;.

MutationTaster

Benign

0.71

D;D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.033

Sift

Uncertain

0.014

D;D;D;D

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.28

B;B;B;.

Vest4

0.21

MutPred

0.23

.;.;Gain of solvent accessibility (P = 0.0411);.;

MVP

0.068

MPC

0.72

ClinPred

0.56

GERP RS

5.6

Varity_R

0.10

gMVP

0.32

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