Genetic Variant SEPTIN12:p.Val158Val (chr16-4783969-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_144605.5(SEPTIN12):c.474G>A(p.Val158Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,613,832 control chromosomes in the GnomAD database, including 62,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5019 hom., cov: 32)

Exomes 𝑓: 0.27 ( 57084 hom. )

Consequence

SEPTIN12
NM_144605.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 0.0850

Publications

30 publications found

Variant links:

Genes affected

SEPTIN12 (HGNC:26348): (septin 12) This gene encodes a guanine-nucleotide binding protein and member of the septin family of cytoskeletal GTPases. Septins play important roles in cytokinesis, exocytosis, embryonic development, and membrane dynamics. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SEPTIN12 Gene-Disease associations (from GenCC):

non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
spermatogenic failure 10
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

SEPTIN12 links:

ENSG00000285952 (HGNC:):

ENSG00000285952 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 16-4783969-C-T is Benign according to our data. Variant chr16-4783969-C-T is described in ClinVar as Benign. ClinVar VariationId is 37113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN12	NM_144605.5 link	c.474G>A	p.Val158Val	synonymous_variant	Exon 5 of 10	ENST00000268231.13	NP_653206.2	Q8IYM1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN12	ENST00000268231.13 link	c.474G>A	p.Val158Val	synonymous_variant	Exon 5 of 10	1	NM_144605.5	ENSP00000268231.8		Q8IYM1-1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38077

AN:

152036

Hom.:

4997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.272

GnomAD2 exomes

AF:

0.290

AC:

72791

AN:

251296

AF XY:

0.294

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.338

Gnomad ASJ exome

AF:

0.348

Gnomad EAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.275

AC:

401912

AN:

1461678

Hom.:

57084

Cov.:

AF XY:

0.279

AC XY:

202872

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.193

AC:

6469

AN:

33476

American (AMR)

AF:

0.330

AC:

14774

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

8977

AN:

26132

East Asian (EAS)

AF:

0.327

AC:

12972

AN:

39700

South Asian (SAS)

AF:

0.405

AC:

34906

AN:

86254

European-Finnish (FIN)

AF:

0.193

AC:

10302

AN:

53418

Middle Eastern (MID)

AF:

0.295

AC:

1702

AN:

5768

European-Non Finnish (NFE)

AF:

0.265

AC:

294463

AN:

1111824

Other (OTH)

AF:

0.287

AC:

17347

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16941

33882

50823

67764

84705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10070

20140

30210

40280

50350

<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:

0.251

AC:

38140

AN:

152154

Hom.:

5019

Cov.:

AF XY:

0.250

AC XY:

18605

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.199

AC:

8266

AN:

41534

American (AMR)

AF:

0.281

AC:

4293

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1187

AN:

3468

East Asian (EAS)

AF:

0.317

AC:

1635

AN:

5160

South Asian (SAS)

AF:

0.412

AC:

1978

AN:

4806

European-Finnish (FIN)

AF:

0.171

AC:

1817

AN:

10612

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.267

AC:

18155

AN:

67978

Other (OTH)

AF:

0.274

AC:

578

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1480

2960

4439

5919

7399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.266

Hom.:

11894

Bravo

AF:

0.255

Asia WGS

AF:

0.406

AC:

1409

AN:

3478

EpiCase

AF:

0.273

EpiControl

AF:

0.285

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22479503) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Spermatogenic failure 10

Other:1

Jan 01, 2012

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.3

(source)

DANN

Benign

0.53

PhyloP100

0.085

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.71

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.71

Position offset: 3

DS_DL_spliceai

0.34

Position offset: -38

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over