rs832529

Variant names:

• chr5-56933461-C-T
• rs832529
• NM_001297599.2:c.596-63G>A

Variant summary

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

The NM_001297599.2(MIER3):​c.596-63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 1,428,914 control chromosomes in the GnomAD database, including 265,900 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 (21466 hom., cov: 33)
  • Exomes 𝑓: 0.61 (244434 hom.)
• Consequence: MIER3 NM_001297599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563
• Publications: 13 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=-0.8).
• 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.596-63G>A		intron_variant	Intron 7 of 12	ENST00000381199.8	NP_001284528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIER3	ENST00000381199.8	c.596-63G>A		intron_variant	Intron 7 of 12	1	NM_001297599.2	ENSP00000370596.3

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76549 AN: 152030 Hom.: 21464 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.536

GnomAD4 exome AF: 0.608 AC: 775881 AN: 1276766 Hom.: 244434 AF XY: 0.605 AC XY: 382119 AN XY: 632000

African (AFR) AF: 0.296 AC: 8013 AN: 27044

American (AMR) AF: 0.346 AC: 9566 AN: 27662

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 13519 AN: 20298

East Asian (EAS) AF: 0.117 AC: 4005 AN: 34210

South Asian (SAS) AF: 0.447 AC: 28291 AN: 63222

European-Finnish (FIN) AF: 0.650 AC: 31465 AN: 48390

Middle Eastern (MID) AF: 0.617 AC: 3155 AN: 5114

European-Non Finnish (NFE) AF: 0.649 AC: 647864 AN: 998420

Other (OTH) AF: 0.573 AC: 30003 AN: 52406

GnomAD4 genome AF: 0.503 AC: 76579 AN: 152148 Hom.: 21466 Cov.: 33 AF XY: 0.497 AC XY: 36978 AN XY: 74378

African (AFR) AF: 0.303 AC: 12580 AN: 41522

American (AMR) AF: 0.431 AC: 6585 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2292 AN: 3472

East Asian (EAS) AF: 0.110 AC: 571 AN: 5188

South Asian (SAS) AF: 0.425 AC: 2048 AN: 4824

European-Finnish (FIN) AF: 0.649 AC: 6860 AN: 10568

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43812 AN: 67970

Other (OTH) AF: 0.532 AC: 1123 AN: 2110

Alfa AF: 0.590 Hom.: 20166

Bravo AF: 0.477

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.64
PhyloP100		0.56
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: rs832529; hg19: chr5-56229288; COSMIC: COSV61229502; COSMIC: COSV61229502;