NM_017550.3:c.1144G>T

Variant names:

• chr19-308631-C-A
• rs202163232
• NM_017550.3:c.1144G>T

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.1144G>T​(p.Asp382Tyr) 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. 13/22 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. D382N) 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: 1.09
• Publications: 1 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=0.25547215).

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.1144G>T	p.Asp382Tyr	missense	Exon 12 of 14	NP_060020.1	Q8N344
	MIER2	NM_001387152.1		c.1150G>T	p.Asp384Tyr	missense	Exon 12 of 14	NP_001374081.1
	MIER2	NM_001387153.1		c.1123G>T	p.Asp375Tyr	missense	Exon 12 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.1144G>T	p.Asp382Tyr	missense	Exon 12 of 14	ENSP00000264819.3	Q8N344
	MIER2	ENST00000931432.1		c.1051G>T	p.Asp351Tyr	missense	Exon 11 of 13	ENSP00000601491.1
	MIER2	ENST00000871288.1		c.1018G>T	p.Asp340Tyr	missense	Exon 11 of 13	ENSP00000541347.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.054
Sift	Benign	0.053	T
Sift4G	Uncertain	0.037	D
Polyphen		0.99	D
Vest4		0.39
MutPred		0.31		Gain of catalytic residue at D382 (P = 0.0062)
MVP		0.043
MPC		0.81
ClinPred		0.78	D
GERP RS		3.4
PromoterAI		0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.34
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs202163232; hg19: chr19-308631;