Genetic Variant SEMA6B:p.Asp881Gly (chr19-4543626-T-C) – 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.2642A>G(p.Asp881Gly) 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. Variant has been reported in ClinVar 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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85

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:

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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=0.17240226).

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.2642A>G	p.Asp881Gly	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.2642A>G	p.Asp881Gly	missense	Exon 17 of 17	ENSP00000467290.1	Q9H3T3-1
SEMA6B	ENST00000586965.1	TSL:1	c.1852-530A>G		intron	N/A	ENSP00000465722.1	Q9H3T3-3
SEMA6B	ENST00000676793.2		c.2642A>G	p.Asp881Gly	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:

1080958

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

510796

African (AFR)

AF:

0.00

AC:

AN:

23132

American (AMR)

AF:

0.00

AC:

AN:

8792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14338

East Asian (EAS)

AF:

0.00

AC:

AN:

26800

South Asian (SAS)

AF:

0.00

AC:

AN:

19782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2960

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

920298

Other (OTH)

AF:

0.00

AC:

AN:

43648

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

1.9

PrimateAI

Pathogenic

0.85

Sift4G

Uncertain

0.053

Polyphen

0.0

Vest4

0.24

MutPred

0.12

Gain of methylation at R882 (P = 0.0316)

MVP

0.043

MPC

2.2

ClinPred

0.86

GERP RS

3.9

Varity_R

0.32

gMVP

0.37

Mutation Taster

=86/14

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

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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