3-50159665-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004186.5(SEMA3F):c.43G>C(p.Gly15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,612,550 control chromosomes in the GnomAD database, including 731 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.039 ( 375 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 356 hom. )

Consequence

SEMA3F
NM_004186.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.67

Publications

5 publications found

Variant links:

Genes affected

SEMA3F (HGNC:10728): (semaphorin 3F) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin loop and a C-terminal basic domain. This gene is expressed by the endothelial cells where it was found to act in an autocrine fashion to induce apoptosis, inhibit cell proliferation and survival, and function as an anti-tumorigenic agent. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

SEMA3F Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

SEMA3F links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017032325).

BP6

Variant 3-50159665-G-C is Benign according to our data. Variant chr3-50159665-G-C is described in ClinVar as Benign. ClinVar VariationId is 3057219.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004186.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA3F	NM_004186.5	MANE Select	c.43G>C	p.Gly15Arg	missense	Exon 2 of 19	NP_004177.3
SEMA3F	NM_001318800.2		c.43G>C	p.Gly15Arg	missense	Exon 2 of 18	NP_001305729.1	Q13275-2
SEMA3F	NM_001318798.2		c.-135-27G>C		intron	N/A	NP_001305727.1	C9JPG5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA3F	ENST00000002829.8	TSL:1 MANE Select	c.43G>C	p.Gly15Arg	missense	Exon 2 of 19	ENSP00000002829.3	Q13275-1
SEMA3F	ENST00000434342.5	TSL:1	c.43G>C	p.Gly15Arg	missense	Exon 2 of 18	ENSP00000409859.1	Q13275-2
SEMA3F	ENST00000413852.5	TSL:1	c.-135-27G>C		intron	N/A	ENSP00000388931.1	C9JPG5

Frequencies

GnomAD3 genomes

AF:

0.0386

AC:

5872

AN:

152184

Hom.:

374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.0104

AC:

2589

AN:

249682

AF XY:

0.00763

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.00662

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000619

Gnomad OTH exome

AF:

0.00559

GnomAD4 exome

AF:

0.00413

AC:

6037

AN:

1460248

Hom.:

356

Cov.:

AF XY:

0.00359

AC XY:

2605

AN XY:

726476

show subpopulations

African (AFR)

AF:

0.141

AC:

4721

AN:

33422

American (AMR)

AF:

0.00752

AC:

335

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39520

South Asian (SAS)

AF:

0.000186

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53080

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000333

AC:

370

AN:

1111292

Other (OTH)

AF:

0.00905

AC:

546

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

253

506

758

1011

1264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<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:

0.0387

AC:

5887

AN:

152302

Hom.:

375

Cov.:

AF XY:

0.0369

AC XY:

2749

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.133

AC:

5515

AN:

41528

American (AMR)

AF:

0.0182

AC:

278

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68034

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

259

517

776

1034

1293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.00432

Hom.:

Bravo

AF:

0.0451

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.141

AC:

620

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0126

AC:

1525

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000437

EpiControl

AF:

0.00125

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SEMA3F-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

2.7

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.1

REVEL

Benign

0.14

Sift

Benign

0.14

Sift4G

Benign

0.57

Polyphen

0.98

Vest4

0.54

MutPred

0.47

Loss of loop (P = 0.0128)

MPC

0.27

ClinPred

0.019

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.21

gMVP

0.44

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over