MIER2 p.Val472Leu

Variant names:

• chr19-307321-C-A
• NM_017550.3:c.1414G>T
• MIER2 p.Val472Leu

Your query was ambiguous. Multiple possible variants found:

• chr19-307321-C-A
• chr19-307321-C-G
• chr19-307319-CAC-TAA
• chr19-307319-CAC-AAG
• chr19-307319-CAC-GAG
• chr19-307319-CAC-TAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017550.3(MIER2):​c.1414G>T​(p.Val472Leu) 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. 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. V472M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MIER2 NM_017550.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712
• Publications: 0 publications found

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]

ACMG classification

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=0.08565661).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER2	NM_017550.3	MANE Select	c.1414G>T	p.Val472Leu	missense	Exon 13 of 14	NP_060020.1	Q8N344
	MIER2	NM_001387152.1		c.1420G>T	p.Val474Leu	missense	Exon 13 of 14	NP_001374081.1
	MIER2	NM_001387153.1		c.1393G>T	p.Val465Leu	missense	Exon 13 of 14	NP_001374082.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER2	ENST00000264819.7	TSL:1 MANE Select	c.1414G>T	p.Val472Leu	missense	Exon 13 of 14	ENSP00000264819.3	Q8N344
	MIER2	ENST00000931432.1		c.1321G>T	p.Val441Leu	missense	Exon 12 of 13	ENSP00000601491.1
	MIER2	ENST00000871288.1		c.1288G>T	p.Val430Leu	missense	Exon 12 of 13	ENSP00000541347.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.7
DANN	Benign	0.90
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.71
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.081
Sift	Benign	0.25	T
Sift4G	Benign	1.0	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.26
Mutation Taster		=93/7	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-307321;