chr3-50159632-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_004186.5(SEMA3F):c.10G>A(p.Ala4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000367 in 1,608,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A4A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

SEMA3F
NM_004186.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: -0.0930

Publications

0 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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04064253).

BP6

Variant 3-50159632-G-A is Benign according to our data. Variant chr3-50159632-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2367544.

BS2

High AC in GnomAd4 at 11 AD gene.

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.10G>A	p.Ala4Thr	missense	Exon 2 of 19	NP_004177.3
SEMA3F	NM_001318800.2		c.10G>A	p.Ala4Thr	missense	Exon 2 of 18	NP_001305729.1	Q13275-2
SEMA3F	NM_001318798.2		c.-135-60G>A		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.10G>A	p.Ala4Thr	missense	Exon 2 of 19	ENSP00000002829.3	Q13275-1
SEMA3F	ENST00000434342.5	TSL:1	c.10G>A	p.Ala4Thr	missense	Exon 2 of 18	ENSP00000409859.1	Q13275-2
SEMA3F	ENST00000413852.5	TSL:1	c.-135-60G>A		intron	N/A	ENSP00000388931.1	C9JPG5

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000648

AC:

AN:

247032

AF XY:

0.0000821

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000330

AC:

AN:

1455872

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

724470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33274

American (AMR)

AF:

0.00

AC:

AN:

43968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39132

South Asian (SAS)

AF:

0.00

AC:

AN:

85712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000415

AC:

AN:

1108692

Other (OTH)

AF:

0.0000332

AC:

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000722

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41568

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000434

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

SEMA3F-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.8

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.013

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.58

M_CAP

Benign

0.018

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

-0.093

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.22

REVEL

Benign

0.043

Sift

Benign

0.59

Sift4G

Benign

0.28

Polyphen

0.0050

Vest4

0.13

MVP

0.59

MPC

0.22

ClinPred

0.022

GERP RS

-2.1

Varity_R

0.034

gMVP

0.25

Mutation Taster

=84/16

polymorphism

(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

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