rs2591961

Positions:

• chr5-56942770-A-G
• chr5-56942770-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297599.2(MIER3):​c.181-3753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,028 control chromosomes in the GnomAD database, including 8,804 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 0.33 (8804 hom., cov: 32)
• Consequence: MIER3 NM_001297599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIER3	NM_001297599.2	c.181-3753T>C		intron_variant		ENST00000381199.8	NP_001284528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIER3	ENST00000381199.8	c.181-3753T>C		intron_variant		1	NM_001297599.2	ENSP00000370596	A1
	ENST00000438553.1	n.273+1191A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49625 AN: 151910 Hom.: 8799 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.327 AC: 49657 AN: 152028 Hom.: 8804 Cov.: 32 AF XY: 0.332 AC XY: 24644 AN XY: 74328

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.307

Alfa AF: 0.280 Hom.: 3159

Bravo AF: 0.342

Asia WGS AF: 0.407 AC: 1415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.78

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: rs2591961; hg19: chr5-56238597;