chr15-68945865-G-A

Variant names:

• chr15-68945865-G-A
• rs574070608
• NM_145658.4:c.331G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145658.4(SPESP1):​c.331G>A​(p.Gly111Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPESP1 NM_145658.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047964305).

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.331G>A	p.Gly111Arg	missense	Exon 2 of 2	NP_663633.1	Q6UW49
	SPESP1-NOX5	NM_001184780.2		c.29+15148G>A		intron	N/A	NP_001171709.1
	SPESP1-NOX5	NR_033671.3		n.193+15148G>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.331G>A	p.Gly111Arg	missense	Exon 2 of 2	ENSP00000312284.3	Q6UW49
	SPESP1-NOX5	ENST00000260364.9	TSL:1	c.-109+15148G>A		intron	N/A	ENSP00000454143.1
	SPESP1-NOX5	ENST00000703585.1		c.29+15148G>A		intron	N/A	ENSP00000515387.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.59
DANN	Benign	0.53
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.11
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.060
Sift	Benign	0.41	T
Sift4G	Benign	0.37	T
Polyphen		0.0020	B
Vest4		0.039
MutPred		0.18		Loss of ubiquitination at K112 (P = 0.0284)
MVP		0.014
MPC		0.049
ClinPred		0.047	T
GERP RS		-2.3
Varity_R		0.043
gMVP		0.033

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs574070608; hg19: chr15-69238204;