NM_017550.3:c.1264C>T

Variant names:

• chr19-307471-G-A
• NM_017550.3:c.1264C>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.1264C>T​(p.Pro422Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 7.1e-7 (0 hom.)
• Consequence: MIER2 NM_017550.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• 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=0.16640717).

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.1264C>T	p.Pro422Ser	missense	Exon 13 of 14	NP_060020.1	Q8N344
	MIER2	NM_001387152.1		c.1270C>T	p.Pro424Ser	missense	Exon 13 of 14	NP_001374081.1
	MIER2	NM_001387153.1		c.1243C>T	p.Pro415Ser	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.1264C>T	p.Pro422Ser	missense	Exon 13 of 14	ENSP00000264819.3	Q8N344
	MIER2	ENST00000931432.1		c.1171C>T	p.Pro391Ser	missense	Exon 12 of 13	ENSP00000601491.1
	MIER2	ENST00000871288.1		c.1138C>T	p.Pro380Ser	missense	Exon 12 of 13	ENSP00000541347.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404118 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 692664

African (AFR) AF: 0.00 AC: 0 AN: 32312

American (AMR) AF: 0.00 AC: 0 AN: 39040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22692

East Asian (EAS) AF: 0.00 AC: 0 AN: 38938

South Asian (SAS) AF: 0.00 AC: 0 AN: 77566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1085814

Other (OTH) AF: 0.00 AC: 0 AN: 57996

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.061
Sift	Benign	0.29	T
Sift4G	Benign	0.15	T
Polyphen		0.92	P
Vest4		0.24
MutPred		0.20		Gain of phosphorylation at P422 (P = 0.0134)
MVP		0.12
MPC		0.24
ClinPred		0.37	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.27
Mutation Taster		=100/0	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

hg19: chr19-307471;