rs555185796

Variant names:

• chr19-307384-C-A
• rs555185796
• NM_017550.3:c.1351G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-307384-C-A
• chr19-307384-C-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.1351G>T​(p.Asp451Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,772 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. 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. D451N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MIER2 NM_017550.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=0.118352234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIER2	NM_017550.3	c.1351G>T	p.Asp451Tyr	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.1351G>T	p.Asp451Tyr	missense_variant	Exon 13 of 14	1	NM_017550.3	ENSP00000264819.3
MIER2	ENST00000619835.4	c.343G>T	p.Asp115Tyr	missense_variant	Exon 3 of 4	3		ENSP00000482489.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000428 AC: 1 AN: 233670 Hom.: 0 AF XY: 0.00000787 AC XY: 1 AN XY: 127072

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000948

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454772 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723026

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.5
DANN	Benign	0.77
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.016
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.022	D
Polyphen		0.69	P
Vest4		0.24
MutPred		0.25		Gain of catalytic residue at D451 (P = 0.0109);
MVP		0.043
MPC		0.45
ClinPred		0.095	T
GERP RS		-0.30
Varity_R		0.083
gMVP		0.40

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: rs555185796; hg19: chr19-307384;