Variant X-48008382-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001394298.1(SPACA5):c.152G>T(p.Cys51Phe) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Consequence

SPACA5
NM_001394298.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.44

Variant links:

Genes affected

SPACA5 (HGNC:31353): (sperm acrosome associated 5) Predicted to enable lysozyme activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SPACA5 links:

ZNF630 (HGNC:28855): (zinc finger protein 630) This gene encodes a protein containing an N-terminal Kruppel-associated box-containing (KRAB) domain and 13 Kruppel-type C2H2 zinc finger domains. This gene resides on an area of chromosome X that has been implicated in nonsyndromic X-linked cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ZNF630 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPACA5	NM_001394298.1 linkuse as main transcript	c.152G>T	p.Cys51Phe	missense_variant	2/4	ENST00000376940.4	NP_001381227.1
SPACA5	NM_205856.3 linkuse as main transcript	c.152G>T	p.Cys51Phe	missense_variant	3/5		NP_995328.2	Q96QH8A0A140VJN7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPACA5	ENST00000376940.4 linkuse as main transcript	c.152G>T	p.Cys51Phe	missense_variant	2/4	1	NM_001394298.1	ENSP00000366139.3	Q96QH8
SPACA5	ENST00000304355.9 linkuse as main transcript	c.152G>T	p.Cys51Phe	missense_variant	3/5	1		ENSP00000305847.5	Q96QH8
ZNF630	ENST00000428463.5 linkuse as main transcript	n.*417-4680C>A		intron_variant		2		ENSP00000400030.1	F8WCH7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000477

AC:

AN:

48180

Hom.:

AF XY:

0.00

AC XY:

AN XY:

11444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000418

AC:

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

Sep 10, 2024

The c.152G>T (p.C51F) alteration is located in exon 3 (coding exon 2) of the SPACA5 gene. This alteration results from a G to T substitution at nucleotide position 152, causing the cysteine (C) at amino acid position 51 to be replaced by a phenylalanine (F). 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

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.48

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

T;T

FATHMM_MKL

Uncertain

0.95

M_CAP

Pathogenic

0.67

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

0.28

MutationAssessor

Pathogenic

4.0

H;H

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-11

D;D

REVEL

Pathogenic

0.83

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.85

MutPred

0.88

Gain of catalytic residue at C51 (P = 0.0954);Gain of catalytic residue at C51 (P = 0.0954);

MVP

0.37

ClinPred

0.52

GERP RS

3.3

Varity_R

0.97

gMVP

0.61

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