15-68946268-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145658.4(SPESP1):c.734C>A(p.Thr245Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SPESP1 NM_145658.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.327

Genes affected

SPESP1 (HGNC:15570): (sperm equatorial segment protein 1) The encoded protein is a human alloantigen involved in sperm-egg binding and fusion. [provided by RefSeq, Apr 2010]

NOX5 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04298061).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPESP1	NM_145658.4	c.734C>A	p.Thr245Asn	missense_variant	2/2	ENST00000310673.4
NOX5	NM_001184780.2	c.29+15551C>A		intron_variant
NOX5	NR_033671.3	n.193+15551C>A		intron_variant, non_coding_transcript_variant
NOX5	NR_033672.2	n.193+15551C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPESP1	ENST00000310673.4	c.734C>A	p.Thr245Asn	missense_variant	2/2	1	NM_145658.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

May 03, 2023

The c.734C>A (p.T245N) alteration is located in exon 2 (coding exon 2) of the SPESP1 gene. This alteration results from a C to A substitution at nucleotide position 734, causing the threonine (T) at amino acid position 245 to be replaced by an asparagine (N). 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	0.088
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.058
Dann	Benign	0.39
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.20	N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.94	N
REVEL	Benign	0.0030
Sift	Benign	0.57	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.21		Loss of glycosylation at T245 (P = 0.0534);
MVP		0.030
MPC		0.046
ClinPred		0.046	T
GERP RS		-3.9
Varity_R		0.030
gMVP		0.056

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: chr15-69238607;