Genetic Variant MZT2B:p.Lys24Asn (chr2-130182354-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_025029.5(MZT2B):c.72G>T(p.Lys24Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MZT2B
NM_025029.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.857

Publications

0 publications found

Variant links:

Genes affected

MZT2B (HGNC:25886): (mitotic spindle organizing protein 2B) Located in cytosol; microtubule cytoskeleton; and nucleoplasm. Part of gamma-tubulin large complex. [provided by Alliance of Genome Resources, Apr 2022]

MZT2B links:

SMPD4 (HGNC:32949): (sphingomyelin phosphodiesterase 4) The protein encoded by this gene is a sphingomyelinase that catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide. This gene is activated by DNA damage, cellular stress, and tumor necrosis factor, but it is downregulated by wild-type p53. The encoded protein localizes to the endoplasmic reticulum and Golgi network. [provided by RefSeq, Mar 2017]

SMPD4 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)

SMPD4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4034601).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025029.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MZT2B	NM_025029.5	MANE Select	c.72G>T	p.Lys24Asn	missense	Exon 1 of 3	NP_079305.2
MZT2B	NM_001330282.2		c.72G>T	p.Lys24Asn	missense	Exon 1 of 4	NP_001317211.1	B8ZZ87
MZT2B	NM_001330284.2		c.72G>T	p.Lys24Asn	missense	Exon 1 of 2	NP_001317213.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MZT2B	ENST00000281871.11	TSL:1 MANE Select	c.72G>T	p.Lys24Asn	missense	Exon 1 of 3	ENSP00000281871.7	Q6NZ67
SMPD4	ENST00000409031.5	TSL:1	c.-753C>A		5_prime_UTR	Exon 1 of 20	ENSP00000386531.1	Q9NXE4-1
MZT2B	ENST00000409255.1	TSL:5	c.72G>T	p.Lys24Asn	missense	Exon 1 of 4	ENSP00000386419.1	B8ZZ87

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1385180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683838

African (AFR)

AF:

0.00

AC:

AN:

30740

American (AMR)

AF:

0.00

AC:

AN:

35748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24958

East Asian (EAS)

AF:

0.00

AC:

AN:

35348

South Asian (SAS)

AF:

0.00

AC:

AN:

78938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4094

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078620

Other (OTH)

AF:

0.00

AC:

AN:

57680

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.6

PhyloP100

0.86

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-2.2

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.28

MutPred

0.47

Loss of methylation at K24 (P = 0.0258)

MVP

0.082

MPC

1.4

ClinPred

0.96

GERP RS

3.3

PromoterAI

0.0063

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.66

gMVP

0.65

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over