Genetic Variant NM_001085365.2:c.319+573T>C (chr2-131491303-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001085365.2(MZT2A):c.319+573T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 287,440 control chromosomes in the GnomAD database, including 26,338 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 0.44 ( 17041 hom., cov: 32)

Exomes 𝑓: 0.34 ( 9297 hom. )

Consequence

MZT2A
NM_001085365.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.630

Variant links:

Genes affected

MZT2A (HGNC:33187): (mitotic spindle organizing protein 2A) Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MZT2A links:

MIR4784 (HGNC:41580): (microRNA 4784) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4784 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MZT2A	NM_001085365.2 link	c.319+573T>C		intron_variant	Intron 2 of 2	ENST00000309451.7	NP_001078834.1	Q6P582

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MZT2A	ENST00000309451.7 link	c.319+573T>C		intron_variant	Intron 2 of 2	1	NM_001085365.2	ENSP00000311500.6		Q6P582

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

66075

AN:

151600

Hom.:

16987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.658

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.552

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.766

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.339

AC:

46008

AN:

135724

Hom.:

9297

Cov.:

AF XY:

0.344

AC XY:

24610

AN XY:

71618

show subpopulations

Gnomad4 AFR exome

AF:

0.651

Gnomad4 AMR exome

AF:

0.592

Gnomad4 ASJ exome

AF:

0.394

Gnomad4 EAS exome

AF:

0.755

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.315

Gnomad4 NFE exome

AF:

0.264

Gnomad4 OTH exome

AF:

0.331

GnomAD4 genome

AF:

0.436

AC:

66197

AN:

151716

Hom.:

17041

Cov.:

AF XY:

0.444

AC XY:

32911

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.659

Gnomad4 AMR

AF:

0.552

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.766

Gnomad4 SAS

AF:

0.412

Gnomad4 FIN

AF:

0.319

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.453

Alfa

AF:

0.315

Hom.:

10351

Bravo

AF:

0.467

Asia WGS

AF:

0.583

AC:

2025

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

4.7

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over