X-48008530-T-G

Position:

• chrX-48008530-T-G

Variant summary

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

The NM_001394298.1(SPACA5):​c.300T>G​(p.Cys100Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: SPACA5 NM_001394298.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.868

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.988

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPACA5	NM_001394298.1	c.300T>G	p.Cys100Trp	missense_variant	2/4	ENST00000376940.4	NP_001381227.1
SPACA5	NM_205856.3	c.300T>G	p.Cys100Trp	missense_variant	3/5		NP_995328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPACA5	ENST00000376940.4	c.300T>G	p.Cys100Trp	missense_variant	2/4	1	NM_001394298.1	ENSP00000366139	P1
SPACA5	ENST00000304355.9	c.300T>G	p.Cys100Trp	missense_variant	3/5	1		ENSP00000305847	P1
ZNF630	ENST00000428463.5	c.*417-4828A>C		intron_variant, NMD_transcript_variant		2		ENSP00000400030

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.300T>G (p.C100W) alteration is located in exon 3 (coding exon 2) of the SPACA5 gene. This alteration results from a T to G substitution at nucleotide position 300, causing the cysteine (C) at amino acid position 100 to be replaced by a tryptophan (W). 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	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;T
FATHMM_MKL	Benign	0.42	N
M_CAP	Pathogenic	0.65	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Pathogenic	4.0	H;H
MutationTaster	Benign	0.65	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-11	D;D
REVEL	Uncertain	0.61
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.83
MutPred		0.89		Loss of catalytic residue at M98 (P = 0.0083);Loss of catalytic residue at M98 (P = 0.0083);
MVP		0.59
ClinPred		1.0	D
GERP RS		-0.79
Varity_R		0.96
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-47867928;