Genetic Variant NM_022827.4:c.1495T>A (chr17-50551109-T-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_022827.4(SPATA20):c.1495T>A(p.Ser499Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,612,064 control chromosomes in the GnomAD database, including 75,652 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 0.39 ( 14902 hom., cov: 33)

Exomes 𝑓: 0.27 ( 60750 hom. )

Consequence

SPATA20
NM_022827.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.106

Publications

41 publications found

Variant links:

Genes affected

SPATA20 (HGNC:26125): (spermatogenesis associated 20) Predicted to be involved in carbohydrate metabolic process; cell differentiation; and spermatogenesis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SPATA20 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=3.3013168E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA20	NM_022827.4 link	c.1495T>A	p.Ser499Thr	missense_variant	Exon 12 of 17	ENST00000006658.11	NP_073738.2	Q8TB22-2
SPATA20	NM_001258372.2 link	c.1447T>A	p.Ser483Thr	missense_variant	Exon 11 of 16		NP_001245301.1	Q8TB22-1
SPATA20	NM_001258373.2 link	c.1315T>A	p.Ser439Thr	missense_variant	Exon 12 of 17		NP_001245302.1	Q8TB22-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA20	ENST00000006658.11 link	c.1495T>A	p.Ser499Thr	missense_variant	Exon 12 of 17	1	NM_022827.4	ENSP00000006658.6		Q8TB22-2

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59944

AN:

152006

Hom.:

14853

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.388

GnomAD2 exomes

AF:

0.304

AC:

75382

AN:

248364

AF XY:

0.288

show subpopulations

Gnomad AFR exome

AF:

0.705

Gnomad AMR exome

AF:

0.421

Gnomad ASJ exome

AF:

0.447

Gnomad EAS exome

AF:

0.0974

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.314

GnomAD4 exome

AF:

0.274

AC:

399709

AN:

1459940

Hom.:

60750

Cov.:

AF XY:

0.269

AC XY:

195553

AN XY:

726250

show subpopulations

African (AFR)

AF:

0.718

AC:

24036

AN:

33468

American (AMR)

AF:

0.414

AC:

18477

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

11467

AN:

26134

East Asian (EAS)

AF:

0.0854

AC:

3391

AN:

39698

South Asian (SAS)

AF:

0.180

AC:

15512

AN:

86210

European-Finnish (FIN)

AF:

0.267

AC:

13966

AN:

52264

Middle Eastern (MID)

AF:

0.364

AC:

1972

AN:

5418

European-Non Finnish (NFE)

AF:

0.263

AC:

292372

AN:

1111792

Other (OTH)

AF:

0.307

AC:

18516

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

16323

32645

48968

65290

81613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9896

19792

29688

39584

49480

<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:

0.395

AC:

60049

AN:

152124

Hom.:

14902

Cov.:

AF XY:

0.389

AC XY:

28942

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.700

AC:

29033

AN:

41490

American (AMR)

AF:

0.406

AC:

6206

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1485

AN:

3468

East Asian (EAS)

AF:

0.104

AC:

536

AN:

5178

South Asian (SAS)

AF:

0.180

AC:

869

AN:

4830

European-Finnish (FIN)

AF:

0.256

AC:

2707

AN:

10584

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17845

AN:

67966

Other (OTH)

AF:

0.396

AC:

836

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1600

3200

4801

6401

8001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.313

Hom.:

2793

Bravo

AF:

0.424

TwinsUK

AF:

0.246

AC:

911

ALSPAC

AF:

0.263

AC:

1013

ESP6500AA

AF:

0.680

AC:

2995

ESP6500EA

AF:

0.274

AC:

2359

ExAC

AF:

0.303

AC:

36666

Asia WGS

AF:

0.225

AC:

785

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.53

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.055

.;.;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.019

T;T;T;T

MetaRNN

Benign

0.0000033

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.045

.;.;N;.

PhyloP100

-0.11

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.43

.;N;N;.

REVEL

Benign

0.011

Sift

Benign

0.67

.;T;T;.

Sift4G

Benign

0.57

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.033

MPC

0.18

ClinPred

0.0054

GERP RS

-6.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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