15-68945622-G-A

Variant names:

• chr15-68945622-G-A
• rs758010802
• NM_145658.4:c.88G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145658.4(SPESP1):​c.88G>A​(p.Glu30Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,428,456 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E30Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SPESP1 NM_145658.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• Publications: 0 publications found

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]

SPESP1-NOX5 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145658.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPESP1	NM_145658.4	MANE Select	c.88G>A	p.Glu30Lys	missense	Exon 2 of 2	NP_663633.1	Q6UW49
	SPESP1-NOX5	NM_001184780.2		c.29+14905G>A		intron	N/A	NP_001171709.1
	SPESP1-NOX5	NR_033671.3		n.193+14905G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPESP1	ENST00000310673.4	TSL:1 MANE Select	c.88G>A	p.Glu30Lys	missense	Exon 2 of 2	ENSP00000312284.3	Q6UW49
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.-109+14905G>A		intron	N/A	ENSP00000454143.1
	SPESP1-NOX5	ENST00000703585.1		c.29+14905G>A		intron	N/A	ENSP00000515387.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428456 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 709152

African (AFR) AF: 0.00 AC: 0 AN: 31636

American (AMR) AF: 0.00 AC: 0 AN: 35946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24226

East Asian (EAS) AF: 0.00 AC: 0 AN: 39392

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5588

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101728

Other (OTH) AF: 0.00 AC: 0 AN: 58984

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.32		Gain of methylation at E30 (P = 0.0071)
MVP		0.35
MPC		0.31
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.78
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs758010802; hg19: chr15-69237961; COSMIC: COSV104535907;