Genetic Variant SEMA3B:p.Arg30Ser (chr3-50269328-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001290060.2(SEMA3B):c.88C>A(p.Arg30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,359,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SEMA3B
NM_001290060.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.759

Publications

0 publications found

Variant links:

Genes affected

SEMA3B (HGNC:10724): (semaphorin 3B) The protein encoded by this gene belongs to the class-3 semaphorin/collapsin family, whose members function in growth cone guidance during neuronal development. This family member inhibits axonal extension and has been shown to act as a tumor suppressor by inducing apoptosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

SEMA3B links:

SEMA3B-AS1 (HGNC:49096): (SEMA3B antisense RNA 1 (head to head))

SEMA3B-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25660324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290060.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA3B	NM_001290060.2	MANE Select	c.88C>A	p.Arg30Ser	missense	Exon 1 of 17	NP_001276989.1	Q13214-1
SEMA3B	NM_001290061.1		c.88C>A	p.Arg30Ser	missense	Exon 1 of 17	NP_001276990.1	Q13214
SEMA3B	NM_001435956.1		c.88C>A	p.Arg30Ser	missense	Exon 4 of 20	NP_001422885.1	Q13214-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA3B	ENST00000616701.5	TSL:1 MANE Select	c.88C>A	p.Arg30Ser	missense	Exon 1 of 17	ENSP00000484146.1	Q13214-1
SEMA3B	ENST00000611067.4	TSL:1	c.88C>A	p.Arg30Ser	missense	Exon 1 of 17	ENSP00000480680.1	A0A0C4DGV8
SEMA3B	ENST00000433753.4	TSL:1	c.88C>A	p.Arg30Ser	missense	Exon 1 of 17	ENSP00000485281.1	Q13214-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1359932

Hom.:

Cov.:

AF XY:

0.00000298

AC XY:

AN XY:

670518

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29682

American (AMR)

AF:

0.00

AC:

AN:

27314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23320

East Asian (EAS)

AF:

0.00

AC:

AN:

35448

South Asian (SAS)

AF:

0.00

AC:

AN:

75744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39768

Middle Eastern (MID)

AF:

0.000195

AC:

AN:

5132

European-Non Finnish (NFE)

AF:

9.37e-7

AC:

AN:

1067152

Other (OTH)

AF:

0.00

AC:

AN:

56372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.21

Eigen

Benign

0.073

Eigen_PC

Benign

0.0027

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.84

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.56

PhyloP100

0.76

PrimateAI

Uncertain

0.66

Sift4G

Uncertain

0.010

Polyphen

0.99

Vest4

0.33

MutPred

0.54

Loss of methylation at R30 (P = 0.0252)

MVP

0.33

ClinPred

0.85

GERP RS

3.9

PromoterAI

0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.21

gMVP

0.94

Mutation Taster

=95/5

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over