19-307471-G-A

Position:

• chr19-307471-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000264819.7(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. 15/21 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 ENST00000264819.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16640717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIER2	NM_017550.3	c.1264C>T	p.Pro422Ser	missense_variant	13/14	ENST00000264819.7	NP_060020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIER2	ENST00000264819.7	c.1264C>T	p.Pro422Ser	missense_variant	13/14	1	NM_017550.3	ENSP00000264819	P1
MIER2	ENST00000619835.4	c.259C>T	p.Pro87Ser	missense_variant	3/4	3		ENSP00000482489

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.21e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.1264C>T (p.P422S) alteration is located in exon 13 (coding exon 13) of the MIER2 gene. This alteration results from a C to T substitution at nucleotide position 1264, causing the proline (P) at amino acid position 422 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	N
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-307471;