dbSNP rs587728978: SEMA3B:p.Ala4Asp (chr3-50269251-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001290060.2(SEMA3B):c.11C>A(p.Ala4Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A4A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SEMA3B
NM_001290060.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76

Publications

1 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.11C>A	p.Ala4Asp	missense	Exon 1 of 17	NP_001276989.1	Q13214-1
SEMA3B	NM_001290061.1		c.11C>A	p.Ala4Asp	missense	Exon 1 of 17	NP_001276990.1	Q13214
SEMA3B	NM_001435956.1		c.11C>A	p.Ala4Asp	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.11C>A	p.Ala4Asp	missense	Exon 1 of 17	ENSP00000484146.1	Q13214-1
SEMA3B	ENST00000611067.4	TSL:1	c.11C>A	p.Ala4Asp	missense	Exon 1 of 17	ENSP00000480680.1	A0A0C4DGV8
SEMA3B	ENST00000433753.4	TSL:1	c.11C>A	p.Ala4Asp	missense	Exon 1 of 17	ENSP00000485281.1	Q13214-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1383924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683078

African (AFR)

AF:

0.00

AC:

AN:

31566

American (AMR)

AF:

0.00

AC:

AN:

35668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25140

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5588

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078276

Other (OTH)

AF:

0.00

AC:

AN:

57854

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Benign

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.073

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.70

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.96

PhyloP100

2.8

PrimateAI

Uncertain

0.72

Sift4G

Benign

0.086

Polyphen

0.0

Vest4

0.65

MutPred

0.62

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.43

ClinPred

0.72

GERP RS

3.1

PromoterAI

-0.055

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.16

gMVP

0.74

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over