Variant 2-130182451-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000409031.5(SMPD4):c.-850T>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000356 in 1,403,900 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000036 ( 0 hom. )

Consequence

SMPD4
ENST00000409031.5 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.9938

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

Variant links:

Genes affected

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 links:

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:

MZT2B (HGNC:):

MZT2B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MZT2B	NM_025029.5 linkuse as main transcript	c.169A>C	p.Lys57Gln	missense_variant, splice_region_variant	1/3	ENST00000281871.11	NP_079305.2	Q6NZ67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MZT2B	ENST00000281871.11 linkuse as main transcript	c.169A>C	p.Lys57Gln	missense_variant, splice_region_variant	1/3	1	NM_025029.5	ENSP00000281871.7		Q6NZ67

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000356

AC:

AN:

1403900

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

693310

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000369

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.169A>C (p.K57Q) alteration is located in exon 1 (coding exon 1) of the MZT2B gene. This alteration results from a A to C substitution at nucleotide position 169, causing the lysine (K) at amino acid position 57 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Benign

0.91

DEOGEN2

Benign

0.19

T;.;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.92

D;D;T

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.7

M;.;.

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0070

D;D;T

Sift4G

Uncertain

0.014

D;D;T

Polyphen

0.82

P;.;.

Vest4

0.48

MutPred

0.41

Loss of ubiquitination at K57 (P = 0.011);Loss of ubiquitination at K57 (P = 0.011);.;

MVP

0.043

MPC

2.8

ClinPred

0.95

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.60

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over