19-307171-C-A

Variant names:

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

Variant summary

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

The NM_017550.3(MIER2):​c.1564G>T​(p.Ala522Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000504 in 1,588,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: MIER2 NM_017550.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51

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=0.0862633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIER2	NM_017550.3	c.1564G>T	p.Ala522Ser	missense_variant	Exon 13 of 14	ENST00000264819.7	NP_060020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIER2	ENST00000264819.7	c.1564G>T	p.Ala522Ser	missense_variant	Exon 13 of 14	1	NM_017550.3	ENSP00000264819.3
MIER2	ENST00000619835.4	c.556G>T	p.Ala186Ser	missense_variant	Exon 3 of 4	3		ENSP00000482489.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000488 AC: 7 AN: 1435882 Hom.: 0 Cov.: 32 AF XY: 0.00000843 AC XY: 6 AN XY: 711538

Gnomad4 AFR exome AF: 0.0000906

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: 9.10e-7

Gnomad4 OTH exome AF: 0.0000337

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1564G>T (p.A522S) alteration is located in exon 13 (coding exon 13) of the MIER2 gene. This alteration results from a G to T substitution at nucleotide position 1564, causing the alanine (A) at amino acid position 522 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	0.087
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.031
Sift	Benign	0.99	T
Sift4G	Benign	0.60	T
Polyphen		0.44	B
Vest4		0.10
MutPred		0.28		Gain of disorder (P = 0.0587);
MVP		0.16
MPC		0.23
ClinPred		0.34	T
GERP RS		3.0
Varity_R		0.019
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs1222879541; hg19: chr19-307171;