19-307507-C-A

Variant summary

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

The NM_017550.3(MIER2):​c.1228G>T​(p.Gly410Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MIER2
NM_017550.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0870
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]

Genome browser will be placed here

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=0.17453927).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MIER2NM_017550.3 linkc.1228G>T p.Gly410Cys missense_variant Exon 13 of 14 ENST00000264819.7 NP_060020.1 Q8N344

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MIER2ENST00000264819.7 linkc.1228G>T p.Gly410Cys missense_variant Exon 13 of 14 1 NM_017550.3 ENSP00000264819.3 Q8N344
MIER2ENST00000619835.4 linkc.220G>T p.Gly74Cys missense_variant Exon 3 of 4 3 ENSP00000482489.2 A0A087WZA4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1363660
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
669136
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1228G>T (p.G410C) alteration is located in exon 13 (coding exon 13) of the MIER2 gene. This alteration results from a G to T substitution at nucleotide position 1228, causing the glycine (G) at amino acid position 410 to be replaced by a cysteine (C). 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
0.073
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.039
T
Eigen
Benign
-0.81
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.051
N
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.12
Sift
Benign
0.060
T
Sift4G
Benign
0.088
T
Polyphen
0.99
D
Vest4
0.15
MutPred
0.18
Loss of glycosylation at T407 (P = 0.1921);
MVP
0.043
MPC
0.57
ClinPred
0.50
D
GERP RS
-3.5
Varity_R
0.097
gMVP
0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-307507; API