X-48008513-C-G

Position:

• chrX-48008513-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001394298.1(SPACA5):​c.283C>G​(p.Leu95Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign 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: 0.742

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16013989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPACA5	NM_001394298.1	c.283C>G	p.Leu95Val	missense_variant	2/4	ENST00000376940.4	NP_001381227.1
SPACA5	NM_205856.3	c.283C>G	p.Leu95Val	missense_variant	3/5		NP_995328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPACA5	ENST00000376940.4	c.283C>G	p.Leu95Val	missense_variant	2/4	1	NM_001394298.1	ENSP00000366139	P1
SPACA5	ENST00000304355.9	c.283C>G	p.Leu95Val	missense_variant	3/5	1		ENSP00000305847	P1
ZNF630	ENST00000428463.5	c.*417-4811G>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

Feb 01, 2023

The c.283C>G (p.L95V) alteration is located in exon 3 (coding exon 2) of the SPACA5 gene. This alteration results from a C to G substitution at nucleotide position 283, causing the leucine (L) at amino acid position 95 to be replaced by a valine (V). 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	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.013	T;T
FATHMM_MKL	Benign	0.59	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	0.91	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.033
Sift	Benign	0.41	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.018	B;B
Vest4		0.19
MutPred		0.30		Gain of methylation at K93 (P = 0.1185);Gain of methylation at K93 (P = 0.1185);
MVP		0.46
ClinPred		0.30	T
GERP RS		2.1
Varity_R		0.17
gMVP		0.10

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-47867911;