rs930421

Positions:

• chr2-42754099-A-G

Variant summary

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

The NM_001330442.2(MTA3):​c.*700A>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 0.334 in 985,122 control chromosomes in the GnomAD database, including 55,368 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 0.35 (9325 hom., cov: 32)
  • Exomes 𝑓: 0.33 (46043 hom.)
• Consequence: MTA3 NM_001330442.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

Genes affected

MTA3 (HGNC:23784): (metastasis associated 1 family member 3) Predicted to enable histone deacetylase binding activity; transcription coactivator activity; and transcription corepressor activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleoplasm. Part of NuRD 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTA3	NM_001330442.2	c.*700A>G		3_prime_UTR_variant	17/17	ENST00000405094.2	NP_001317371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTA3	ENST00000405094.2	c.*700A>G		3_prime_UTR_variant	17/17	5	NM_001330442.2	ENSP00000385823.1
MTA3	ENST00000406652.5	c.*700A>G		3_prime_UTR_variant	17/17	1		ENSP00000384249.1
MTA3	ENST00000405592.5	c.*700A>G		3_prime_UTR_variant	18/18	2		ENSP00000383973.1
MTA3	ENST00000409019.5	n.*783A>G		downstream_gene_variant		5		ENSP00000386763.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52589 AN: 151864 Hom.: 9328 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.332 AC: 276398 AN: 833136 Hom.: 46043 Cov.: 29 AF XY: 0.332 AC XY: 127761 AN XY: 384738

Gnomad4 AFR exome AF: 0.404

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.346 AC: 52616 AN: 151986 Hom.: 9325 Cov.: 32 AF XY: 0.344 AC XY: 25560 AN XY: 74258

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.345

Alfa AF: 0.326 Hom.: 10963

Bravo AF: 0.362

Asia WGS AF: 0.290 AC: 1007 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	2.4
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs930421; hg19: chr2-42981239;