rs252890

Variant names:

• chr5-56930583-T-C
• rs252890
• NM_001297599.2:c.829+81A>G

Variant summary

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

The NM_001297599.2(MIER3):​c.829+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,134,892 control chromosomes in the GnomAD database, including 200,211 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 0.50 (21457 hom., cov: 31)
  • Exomes 𝑓: 0.59 (178754 hom.)
• Consequence: MIER3 NM_001297599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519
• Publications: 16 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIER3	NM_001297599.2	c.829+81A>G		intron_variant	Intron 9 of 12	ENST00000381199.8	NP_001284528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIER3	ENST00000381199.8	c.829+81A>G		intron_variant	Intron 9 of 12	1	NM_001297599.2	ENSP00000370596.3

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76529 AN: 151830 Hom.: 21455 Cov.: 31

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.571

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.536

GnomAD4 exome AF: 0.588 AC: 577515 AN: 982942 Hom.: 178754 AF XY: 0.584 AC XY: 297930 AN XY: 509856

African (AFR) AF: 0.305 AC: 7242 AN: 23780

American (AMR) AF: 0.348 AC: 14964 AN: 43020

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 15069 AN: 22608

East Asian (EAS) AF: 0.115 AC: 4298 AN: 37314

South Asian (SAS) AF: 0.448 AC: 34058 AN: 75982

European-Finnish (FIN) AF: 0.650 AC: 33808 AN: 51982

Middle Eastern (MID) AF: 0.618 AC: 2971 AN: 4804

European-Non Finnish (NFE) AF: 0.648 AC: 439949 AN: 679104

Other (OTH) AF: 0.567 AC: 25156 AN: 44348

GnomAD4 genome AF: 0.504 AC: 76560 AN: 151950 Hom.: 21457 Cov.: 31 AF XY: 0.498 AC XY: 36966 AN XY: 74292

African (AFR) AF: 0.305 AC: 12620 AN: 41440

American (AMR) AF: 0.430 AC: 6568 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2288 AN: 3468

East Asian (EAS) AF: 0.110 AC: 566 AN: 5168

South Asian (SAS) AF: 0.425 AC: 2047 AN: 4812

European-Finnish (FIN) AF: 0.649 AC: 6858 AN: 10572

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.645 AC: 43780 AN: 67908

Other (OTH) AF: 0.532 AC: 1126 AN: 2116

Alfa AF: 0.610 Hom.: 23669

Bravo AF: 0.478

Asia WGS AF: 0.298 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.5
DANN	Benign	0.79
PhyloP100		0.52
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: rs252890; hg19: chr5-56226410; COSMIC: COSV67082757; COSMIC: COSV67082757;