Variant 5-80320822-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032567.4(SPZ1):c.607G>A(p.Ala203Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 1,614,066 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

SPZ1
NM_032567.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.313

Variant links:

Genes affected

SPZ1 (HGNC:30721): (spermatogenic leucine zipper 1) This gene encodes a bHLH-zip transcription factor which functions in the mitogen-activate protein kinase (MAPK) signaling pathway. Because of its role in the upregulation of cell proliferation and tumorigenesis, this gene may serve as a target for Ras-induced tumor treatments. [provided by RefSeq, Oct 2011]

SPZ1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073192716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPZ1	NM_032567.4 linkuse as main transcript	c.607G>A	p.Ala203Thr	missense_variant	1/1	ENST00000296739.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPZ1	ENST00000296739.6 linkuse as main transcript	c.607G>A	p.Ala203Thr	missense_variant	1/1		NM_032567.4	P1
SPZ1	ENST00000511881.1 linkuse as main transcript	c.607G>A	p.Ala203Thr	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000489

AC:

122

AN:

249278

Hom.:

AF XY:

0.000443

AC XY:

AN XY:

135292

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00537

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000322

AC:

470

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

227

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00543

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000591

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000505

Hom.:

Bravo

AF:

0.000661

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.000491

AC:

ExAC

AF:

0.000431

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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

Oct 18, 2021

The c.607G>A (p.A203T) alteration is located in exon 1 (coding exon 1) of the SPZ1 gene. This alteration results from a G to A substitution at nucleotide position 607, causing the alanine (A) at amino acid position 203 to be replaced by a threonine (T). 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

Benign

0.093

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.82

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.080

N;N

REVEL

Benign

0.0080

Sift

Benign

0.16

T;T

Sift4G

Benign

0.072

T;T

Polyphen

0.28

.;B

Vest4

0.059

MVP

0.030

MPC

0.034

ClinPred

0.0011

GERP RS

0.26

Varity_R

0.026

gMVP

0.040

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over