Genetic Variant SEMA6B:p.Ala865Thr (chr19-4543675-C-T) – 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_032108.4(SEMA6B):c.2593G>A(p.Ala865Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A865G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SEMA6B
NM_032108.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

0 publications found

Variant links:

Genes affected

SEMA6B (HGNC:10739): (semaphorin 6B) This gene encodes a member of the semaphorin family, a group of proteins characterized by the presence of a conserved semaphorin (sema) domain. Whereas some semaphorins are transmembrane proteins, others are secreted. Semaphorins play a major role in axon guidance. The protein encoded by this gene may be involved in both peripheral and central nervous system development. [provided by RefSeq, Jul 2008]

SEMA6B Gene-Disease associations (from GenCC):

progressive myoclonus epilepsy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
epilepsy, progressive myoclonic, 11
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
intellectual disability
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

SEMA6B links:

Genome browser will be placed here

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=0.078219324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032108.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6B	NM_032108.4	MANE Select	c.2593G>A	p.Ala865Thr	missense	Exon 17 of 17	NP_115484.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA6B	ENST00000586582.6	TSL:1 MANE Select	c.2593G>A	p.Ala865Thr	missense	Exon 17 of 17	ENSP00000467290.1	Q9H3T3-1
SEMA6B	ENST00000586965.1	TSL:1	c.1852-579G>A		intron	N/A	ENSP00000465722.1	Q9H3T3-3
SEMA6B	ENST00000676793.2		c.2593G>A	p.Ala865Thr	missense	Exon 17 of 17	ENSP00000503414.1	Q9H3T3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1078440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

509222

African (AFR)

AF:

0.00

AC:

AN:

22886

American (AMR)

AF:

0.00

AC:

AN:

8386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14306

East Asian (EAS)

AF:

0.00

AC:

AN:

26480

South Asian (SAS)

AF:

0.00

AC:

AN:

19528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2944

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

919242

Other (OTH)

AF:

0.00

AC:

AN:

43562

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-0.058

PrimateAI

Pathogenic

0.83

Sift4G

Benign

0.10

Polyphen

0.0040

Vest4

0.14

MutPred

0.15

Gain of phosphorylation at A865 (P = 0.0502)

MVP

0.043

MPC

1.8

ClinPred

0.37

GERP RS

0.40

Varity_R

0.054

gMVP

0.30

Mutation Taster

=87/13

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