rs702681

Variant names:

• chr5-56922202-C-T
• rs702681
• NM_001297599.2:c.*926G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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]

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

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER3	NM_001297599.2	MANE Select	c.*926G>A		3_prime_UTR	Exon 13 of 13	NP_001284528.1	Q7Z3K6-1
	MIER3	NM_001297598.2		c.*926G>A		3_prime_UTR	Exon 13 of 13	NP_001284527.1	Q7Z3K6-2
	MIER3	NM_152622.5		c.*926G>A		3_prime_UTR	Exon 13 of 13	NP_689835.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER3	ENST00000381199.8	TSL:1 MANE Select	c.*926G>A		3_prime_UTR	Exon 13 of 13	ENSP00000370596.3	Q7Z3K6-1
	MIER3	ENST00000381226.7	TSL:1	c.*926G>A		3_prime_UTR	Exon 13 of 13	ENSP00000370624.3	Q7Z3K6-2
	MIER3	ENST00000381213.7	TSL:1	c.*926G>A		3_prime_UTR	Exon 13 of 13	ENSP00000370611.3	Q7Z3K6-3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.762 AC: 314 AN: 412

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 4 AN: 6

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.463 AC: 19187 AN: 41476

American (AMR) AF: 0.521 AC: 7960 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2623 AN: 3466

East Asian (EAS) AF: 0.253 AC: 1308 AN: 5178

South Asian (SAS) AF: 0.529 AC: 2553 AN: 4824

European-Finnish (FIN) AF: 0.733 AC: 7760 AN: 10592

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50057 AN: 67980

Other (OTH) AF: 0.641 AC: 1356 AN: 2116

Alfa AF: 0.682 Hom.: 23647

Bravo AF: 0.593

Asia WGS AF: 0.403 AC: 1402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.3
DANN	Benign	0.79
PhyloP100		-0.088
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: rs702681; hg19: chr5-56218029;