rs702681

chr5-56922202-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001297599.2(MIER3):c.*926G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,542 control chromosomes in the GnomAD database, including 30,528 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 0.62 (30407 hom., cov: 33)
  • Exomes 𝑓: 0.76 (121 hom.)
• Consequence: MIER3 NM_001297599.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

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]

SETD9 (HGNC:28508): (SET domain containing 9) Predicted to enable lysine N-methyltransferase activity. Predicted to be involved in regulation of signal transduction by p53 class mediator. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIER3	NM_001297599.2	c.*926G>A		3_prime_UTR_variant	13/13	ENST00000381199.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIER3	ENST00000381199.8	c.*926G>A		3_prime_UTR_variant	13/13	1	NM_001297599.2	A1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93539 AN: 152002 Hom.: 30398 Cov.: 33

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.646

GnomAD4 exome AF: 0.761 AC: 321 AN: 422 Hom.: 121 Cov.: 0 AF XY: 0.754 AC XY: 193 AN XY: 256

Gnomad4 FIN exome AF: 0.762

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.615 AC: 93589 AN: 152120 Hom.: 30407 Cov.: 33 AF XY: 0.609 AC XY: 45265 AN XY: 74378

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.641

Alfa AF: 0.673 Hom.: 15115

Bravo AF: 0.593

Asia WGS AF: 0.403 AC: 1402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	6.3
Dann	Benign	0.79

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: rs702681; hg19: chr5-56218029;