chr5-56941838-C-A

Variant names:

• chr5-56941838-C-A
• rs16886525
• NM_001297599.2:c.181-2821G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297599.2(MIER3):​c.181-2821G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 152,008 control chromosomes in the GnomAD database, including 531 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.081 (531 hom., cov: 32)
• Consequence: MIER3 NM_001297599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 3 publications found

Genes affected

MIER3 (HGNC:26678): (MIER family member 3) Predicted to enable histone deacetylase binding activity and transcription corepressor activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000235635 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297599.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER3	NM_001297599.2	MANE Select	c.181-2821G>T		intron	N/A	NP_001284528.1
	MIER3	NM_001297598.2		c.196-2821G>T		intron	N/A	NP_001284527.1
	MIER3	NM_152622.5		c.181-2821G>T		intron	N/A	NP_689835.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER3	ENST00000381199.8	TSL:1 MANE Select	c.181-2821G>T		intron	N/A	ENSP00000370596.3
	MIER3	ENST00000381226.7	TSL:1	c.196-2821G>T		intron	N/A	ENSP00000370624.3
	MIER3	ENST00000381213.7	TSL:1	c.181-2821G>T		intron	N/A	ENSP00000370611.3

Frequencies

GnomAD3 genomes AF: 0.0811 AC: 12317 AN: 151890 Hom.: 531 Cov.: 32

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0809

Gnomad ASJ AF: 0.0962

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0829

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.0940

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0811 AC: 12330 AN: 152008 Hom.: 531 Cov.: 32 AF XY: 0.0821 AC XY: 6100 AN XY: 74280

African (AFR) AF: 0.0528 AC: 2187 AN: 41448

American (AMR) AF: 0.0807 AC: 1233 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 334 AN: 3472

East Asian (EAS) AF: 0.141 AC: 728 AN: 5156

South Asian (SAS) AF: 0.102 AC: 491 AN: 4810

European-Finnish (FIN) AF: 0.0829 AC: 875 AN: 10550

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0913 AC: 6210 AN: 67988

Other (OTH) AF: 0.0930 AC: 196 AN: 2108

Alfa AF: 0.0889 Hom.: 537

Bravo AF: 0.0811

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.68
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs16886525; hg19: chr5-56237665;