rs702680

Positions:

• chr5-56924555-T-C

Variant summary

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

The NM_001297599.2(MIER3):​c.925-513A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,106 control chromosomes in the GnomAD database, including 20,978 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 0.49 (20978 hom., cov: 32)
• Consequence: MIER3 NM_001297599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIER3	NM_001297599.2	c.925-513A>G		intron_variant		ENST00000381199.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIER3	ENST00000381199.8	c.925-513A>G		intron_variant		1	NM_001297599.2	A1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74913 AN: 151988 Hom.: 20980 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.493 AC: 74929 AN: 152106 Hom.: 20978 Cov.: 32 AF XY: 0.487 AC XY: 36171 AN XY: 74342

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.523

Alfa AF: 0.528 Hom.: 4050

Bravo AF: 0.465

Asia WGS AF: 0.293 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.4
DANN	Benign	0.67

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: rs702680; hg19: chr5-56220382;