19-307492-C-T

Variant names:

• chr19-307492-C-T
• rs1244153981
• NM_017550.3:c.1243G>A

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.1243G>A​(p.Gly415Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000524 in 1,525,836 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G415E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: MIER2 NM_017550.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• 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=0.074606925).

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.1243G>A	p.Gly415Arg	missense	Exon 13 of 14	NP_060020.1	Q8N344
	MIER2	NM_001387152.1		c.1249G>A	p.Gly417Arg	missense	Exon 13 of 14	NP_001374081.1
	MIER2	NM_001387153.1		c.1222G>A	p.Gly408Arg	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.1243G>A	p.Gly415Arg	missense	Exon 13 of 14	ENSP00000264819.3	Q8N344
	MIER2	ENST00000931432.1		c.1150G>A	p.Gly384Arg	missense	Exon 12 of 13	ENSP00000601491.1
	MIER2	ENST00000871288.1		c.1117G>A	p.Gly373Arg	missense	Exon 12 of 13	ENSP00000541347.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 167104 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000437 AC: 6 AN: 1373688 Hom.: 0 Cov.: 32 AF XY: 0.00000296 AC XY: 2 AN XY: 675198

African (AFR) AF: 0.0000643 AC: 2 AN: 31112

American (AMR) AF: 0.00 AC: 0 AN: 32916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20814

East Asian (EAS) AF: 0.00 AC: 0 AN: 38796

South Asian (SAS) AF: 0.00 AC: 0 AN: 73088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5384

European-Non Finnish (NFE) AF: 0.00000373 AC: 4 AN: 1073682

Other (OTH) AF: 0.00 AC: 0 AN: 56776

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74310

African (AFR) AF: 0.0000241 AC: 1 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.5
DANN	Benign	0.94
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.0
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.046
Sift	Benign	0.063	T
Sift4G	Uncertain	0.033	D
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.36		Gain of solvent accessibility (P = 0.0023)
MVP		0.043
MPC		0.23
ClinPred		0.092	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.17
Mutation Taster		=91/9	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

Other links and lift over

dbSNP: rs1244153981; hg19: chr19-307492; COSMIC: COSV53397495; COSMIC: COSV53397495;