rs3743093

chr15-68946106-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145658.4(SPESP1):c.572G>A(p.Gly191Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,613,776 control chromosomes in the GnomAD database, including 276,493 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.58 (25597 hom., cov: 32)
  • Exomes 𝑓: 0.58 (250896 hom.)
• Consequence: SPESP1 NM_145658.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.6811095E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPESP1	NM_145658.4	c.572G>A	p.Gly191Glu	missense_variant	2/2	ENST00000310673.4
NOX5	NM_001184780.2	c.29+15389G>A		intron_variant
NOX5	NR_033671.3	n.193+15389G>A		intron_variant, non_coding_transcript_variant
NOX5	NR_033672.2	n.193+15389G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPESP1	ENST00000310673.4	c.572G>A	p.Gly191Glu	missense_variant	2/2	1	NM_145658.4	P1
SPESP1	ENST00000560188.1	n.605G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87548 AN: 151888 Hom.: 25577 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.574

GnomAD3 exomes AF: 0.541 AC: 135921 AN: 251170 Hom.: 37751 AF XY: 0.543 AC XY: 73697 AN XY: 135774

Gnomad AFR exome AF: 0.593

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.556

Gnomad EAS exome AF: 0.462

Gnomad SAS exome AF: 0.442

Gnomad FIN exome AF: 0.578

Gnomad NFE exome AF: 0.605

Gnomad OTH exome AF: 0.555

GnomAD4 exome AF: 0.583 AC: 852027 AN: 1461770 Hom.: 250896 Cov.: 62 AF XY: 0.580 AC XY: 421430 AN XY: 727194

Gnomad4 AFR exome AF: 0.594

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.606

Gnomad4 OTH exome AF: 0.575

GnomAD4 genome AF: 0.576 AC: 87601 AN: 152006 Hom.: 25597 Cov.: 32 AF XY: 0.570 AC XY: 42352 AN XY: 74284

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.570

Alfa AF: 0.592 Hom.: 69274

Bravo AF: 0.573

TwinsUK AF: 0.597 AC: 2212

ALSPAC AF: 0.585 AC: 2255

ESP6500AA AF: 0.591 AC: 2602

ESP6500EA AF: 0.607 AC: 5216

ExAC AF: 0.549 AC: 66629

Asia WGS AF: 0.498 AC: 1734 AN: 3478

EpiCase AF: 0.608

EpiControl AF: 0.607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.69
Dann	Benign	0.39
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.000087	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.14	N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.016
Sift	Benign	1.0	T
Sift4G	Benign	0.87	T
Polyphen		0.0	B
Vest4		0.0060
MPC		0.049
ClinPred		0.0082	T
GERP RS		-0.35
Varity_R		0.064
gMVP		0.044

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

LitVar

Other links and lift over

dbSNP: rs3743093; hg19: chr15-69238445; COSMIC: COSV52986310; COSMIC: COSV52986310;