chr5-56921702-T-C

Position:

• chr5-56921702-T-C

Variant summary

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

The ENST00000381199.8(MIER3):​c.*1426A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 152,690 control chromosomes in the GnomAD database, including 656 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 0.091 (655 hom., cov: 33)
  • Exomes 𝑓: 0.099 (1 hom.)
• Consequence: MIER3 ENST00000381199.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826

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=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIER3	NM_001297599.2	c.*1426A>G		3_prime_UTR_variant	13/13	ENST00000381199.8	NP_001284528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIER3	ENST00000381199.8	c.*1426A>G		3_prime_UTR_variant	13/13	1	NM_001297599.2	ENSP00000370596	A1

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13846 AN: 152138 Hom.: 655 Cov.: 33

Gnomad AFR AF: 0.0875

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0914

Gnomad OTH AF: 0.0991

GnomAD4 exome AF: 0.0991 AC: 43 AN: 434 Hom.: 1 Cov.: 0 AF XY: 0.0885 AC XY: 23 AN XY: 260

Gnomad4 FIN exome AF: 0.0967

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0910 AC: 13862 AN: 152256 Hom.: 655 Cov.: 33 AF XY: 0.0918 AC XY: 6837 AN XY: 74452

Gnomad4 AFR AF: 0.0876

Gnomad4 AMR AF: 0.0838

Gnomad4 ASJ AF: 0.0960

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0827

Gnomad4 NFE AF: 0.0915

Gnomad4 OTH AF: 0.0981

Alfa AF: 0.0945 Hom.: 761

Bravo AF: 0.0922

Asia WGS AF: 0.104 AC: 362 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.83

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: rs16886496; hg19: chr5-56217529;