dbSNP rs3743093: SPESP1:p.Gly191Glu (chr15-68946106-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 25597 hom., cov: 32)

Exomes 𝑓: 0.58 ( 250896 hom. )

Consequence

SPESP1
NM_145658.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.151

Publications

30 publications found

Variant links:

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 links:

SPESP1-NOX5 (HGNC:):

SPESP1-NOX5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPESP1	NM_145658.4 link	c.572G>A	p.Gly191Glu	missense_variant	Exon 2 of 2	ENST00000310673.4	NP_663633.1	Q6UW49
SPESP1-NOX5	NM_001184780.2 link	c.29+15389G>A		intron_variant	Intron 1 of 15		NP_001171709.1	Q96PH1-6A3QRJ0
SPESP1-NOX5	NR_033671.3 link	n.193+15389G>A		intron_variant	Intron 1 of 16
SPESP1-NOX5	NR_033672.2 link	n.193+15389G>A		intron_variant	Intron 1 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPESP1	ENST00000310673.4 link	c.572G>A	p.Gly191Glu	missense_variant	Exon 2 of 2	1	NM_145658.4	ENSP00000312284.3		Q6UW49
SPESP1-NOX5	ENST00000703585.1 link	c.29+15389G>A		intron_variant	Intron 1 of 15			ENSP00000515387.1		Q96PH1-6

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87548

AN:

151888

Hom.:

25577

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.541

AC:

135921

AN:

251170

AF XY:

0.543

show subpopulations

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 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.:

AF XY:

0.580

AC XY:

421430

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.594

AC:

19892

AN:

33478

American (AMR)

AF:

0.420

AC:

18771

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

14557

AN:

26134

East Asian (EAS)

AF:

0.465

AC:

18458

AN:

39700

South Asian (SAS)

AF:

0.441

AC:

38032

AN:

86250

European-Finnish (FIN)

AF:

0.577

AC:

30839

AN:

53412

Middle Eastern (MID)

AF:

0.505

AC:

2910

AN:

5768

European-Non Finnish (NFE)

AF:

0.606

AC:

673856

AN:

1111912

Other (OTH)

AF:

0.575

AC:

34712

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

21640

43280

64921

86561

108201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18122

36244

54366

72488

90610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.576

AC:

87601

AN:

152006

Hom.:

25597

Cov.:

AF XY:

0.570

AC XY:

42352

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.595

AC:

24668

AN:

41438

American (AMR)

AF:

0.495

AC:

7558

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.568

AC:

1971

AN:

3472

East Asian (EAS)

AF:

0.464

AC:

2395

AN:

5166

South Asian (SAS)

AF:

0.441

AC:

2129

AN:

4824

European-Finnish (FIN)

AF:

0.574

AC:

6065

AN:

10566

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.602

AC:

40918

AN:

67954

Other (OTH)

AF:

0.570

AC:

1201

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1881

3762

5643

7524

9405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.590

Hom.:

104285

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

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.69

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.017

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.21

MetaRNN

Benign

0.000087

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.14

PhyloP100

0.15

PrimateAI

Benign

0.27

PROVEAN

Benign

1.7

REVEL

Benign

0.016

Sift

Benign

1.0

Sift4G

Benign

0.87

Polyphen

0.0

Vest4

0.0060

MPC

0.049

ClinPred

0.0082

GERP RS

-0.35

Varity_R

0.064

gMVP

0.044

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over