19-311911-C-G

Variant names:

• chr19-311911-C-G
• rs117010939
• NM_017550.3:c.918G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017550.3(MIER2):​c.918G>C​(p.Glu306Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E306E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MIER2 NM_017550.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

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.918G>C	p.Glu306Asp	missense	Exon 10 of 14	NP_060020.1	Q8N344
	MIER2	NM_001387152.1		c.924G>C	p.Glu308Asp	missense	Exon 10 of 14	NP_001374081.1
	MIER2	NM_001387153.1		c.918G>C	p.Glu306Asp	missense	Exon 10 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.918G>C	p.Glu306Asp	missense	Exon 10 of 14	ENSP00000264819.3	Q8N344
	MIER2	ENST00000931432.1		c.825G>C	p.Glu275Asp	missense	Exon 9 of 13	ENSP00000601491.1
	MIER2	ENST00000871288.1		c.792G>C	p.Glu264Asp	missense	Exon 9 of 13	ENSP00000541347.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461742 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111926

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.63
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.31
Sift	Benign	0.046	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.89		Loss of disorder (P = 0.2162)
MVP		0.40
MPC		0.73
ClinPred		0.97	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.74
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

Other links and lift over

dbSNP: rs117010939; hg19: chr19-311911;