chr5-56933461-C-T

Position:

• chr5-56933461-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MIER3	NM_001297599.2	c.596-63G>A		intron_variant		ENST00000381199.8	NP_001284528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIER3	ENST00000381199.8	c.596-63G>A		intron_variant		1	NM_001297599.2	ENSP00000370596	A1

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

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.666

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.573

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

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.532

Alfa AF: 0.582 Hom.: 12274

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

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: rs832529; hg19: chr5-56229288; COSMIC: COSV61229502; COSMIC: COSV61229502;