19-307171-C-G

Variant names:

• chr19-307171-C-G
• rs1222879541
• NM_017550.3:c.1564G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017550.3(MIER2):​c.1564G>C​(p.Ala522Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,435,882 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A522S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MIER2 NM_017550.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31123298).

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.1564G>C	p.Ala522Pro	missense	Exon 13 of 14	NP_060020.1	Q8N344
	MIER2	NM_001387152.1		c.1570G>C	p.Ala524Pro	missense	Exon 13 of 14	NP_001374081.1
	MIER2	NM_001387153.1		c.1543G>C	p.Ala515Pro	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.1564G>C	p.Ala522Pro	missense	Exon 13 of 14	ENSP00000264819.3	Q8N344
	MIER2	ENST00000931432.1		c.1471G>C	p.Ala491Pro	missense	Exon 12 of 13	ENSP00000601491.1
	MIER2	ENST00000871288.1		c.1438G>C	p.Ala480Pro	missense	Exon 12 of 13	ENSP00000541347.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1435882 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 711538

African (AFR) AF: 0.00 AC: 0 AN: 33128

American (AMR) AF: 0.00 AC: 0 AN: 40924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25588

East Asian (EAS) AF: 0.00 AC: 0 AN: 38558

South Asian (SAS) AF: 0.00 AC: 0 AN: 82422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1099414

Other (OTH) AF: 0.00 AC: 0 AN: 59356

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.094
Sift	Benign	0.052	T
Sift4G	Benign	0.11	T
Polyphen		0.96	D
Vest4		0.48
MutPred		0.29		Gain of disorder (P = 0.0727)
MVP		0.12
MPC		0.77
ClinPred		0.72	D
GERP RS		3.0
Varity_R		0.091
gMVP		0.59
Mutation Taster		=87/13	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: rs1222879541; hg19: chr19-307171;