Genetic Variant SPAG16:p.Gln361His (chr2-213862497-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_024532.5(SPAG16):c.1083A>C(p.Gln361His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,613,432 control chromosomes in the GnomAD database, including 117,934 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 0.34 ( 9441 hom., cov: 32)

Exomes 𝑓: 0.38 ( 108493 hom. )

Consequence

SPAG16
NM_024532.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.665

Publications

32 publications found

Variant links:

Genes affected

SPAG16 (HGNC:23225): (sperm associated antigen 16) Cilia and flagella are comprised of a microtubular backbone, the axoneme, which is organized by the basal body and surrounded by plasma membrane. SPAG16 encodes 2 major proteins that associate with the axoneme of sperm tail and the nucleus of postmeiotic germ cells, respectively (Zhang et al., 2007 [PubMed 17699735]).[supplied by OMIM, Jul 2008]

SPAG16 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=8.4257126E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG16	NM_024532.5 link	c.1083A>C	p.Gln361His	missense_variant	Exon 11 of 16	ENST00000331683.10	NP_078808.3	Q8N0X2-1Q4G1A2B4DYB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG16	ENST00000331683.10 link	c.1083A>C	p.Gln361His	missense_variant	Exon 11 of 16	1	NM_024532.5	ENSP00000332592.5		Q8N0X2-1

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52145

AN:

151860

Hom.:

9442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.332

GnomAD2 exomes

AF:

0.390

AC:

97955

AN:

251166

AF XY:

0.393

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.431

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.431

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.382

AC:

558305

AN:

1461454

Hom.:

108493

Cov.:

AF XY:

0.385

AC XY:

279619

AN XY:

727004

show subpopulations

African (AFR)

AF:

0.216

AC:

7226

AN:

33476

American (AMR)

AF:

0.425

AC:

18987

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

7966

AN:

26124

East Asian (EAS)

AF:

0.488

AC:

19357

AN:

39688

South Asian (SAS)

AF:

0.465

AC:

40114

AN:

86246

European-Finnish (FIN)

AF:

0.399

AC:

21299

AN:

53400

Middle Eastern (MID)

AF:

0.348

AC:

2004

AN:

5756

European-Non Finnish (NFE)

AF:

0.377

AC:

419183

AN:

1111670

Other (OTH)

AF:

0.367

AC:

22169

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

17627

35254

52881

70508

88135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13238

26476

39714

52952

66190

<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:

0.343

AC:

52161

AN:

151978

Hom.:

9441

Cov.:

AF XY:

0.350

AC XY:

25998

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.228

AC:

9468

AN:

41454

American (AMR)

AF:

0.399

AC:

6092

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

1078

AN:

3468

East Asian (EAS)

AF:

0.454

AC:

2347

AN:

5168

South Asian (SAS)

AF:

0.477

AC:

2292

AN:

4804

European-Finnish (FIN)

AF:

0.394

AC:

4152

AN:

10542

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.374

AC:

25404

AN:

67948

Other (OTH)

AF:

0.334

AC:

704

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1722

3444

5165

6887

8609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.364

Hom.:

38607

Bravo

AF:

0.333

TwinsUK

AF:

0.371

AC:

1375

ALSPAC

AF:

0.374

AC:

1440

ESP6500AA

AF:

0.229

AC:

1008

ESP6500EA

AF:

0.378

AC:

3250

ExAC

AF:

0.390

AC:

47387

Asia WGS

AF:

0.478

AC:

1664

AN:

3478

EpiCase

AF:

0.371

EpiControl

AF:

0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.26

(source)

DANN

Benign

0.099

DEOGEN2

Benign

0.045

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.23

T;T

MetaRNN

Benign

0.00084

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.8

N;.

PhyloP100

-0.67

PrimateAI

Uncertain

0.49

PROVEAN

Benign

6.7

N;N

REVEL

Benign

0.089

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.079

MutPred

0.22

Loss of methylation at K364 (P = 0.1244);.;

MPC

0.021

ClinPred

0.00030

GERP RS

-1.4

Varity_R

0.034

gMVP

0.34

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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