Genetic Variant SEMA6B:p.Arg656Pro (chr19-4542981-C-G) – 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 ENST00000586965.1(SEMA6B):c.1967G>C(p.Arg656Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000732 in 546,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict 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. R656H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

SEMA6B
ENST00000586965.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

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=0.12998438).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000586965.1. 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.*620G>C		3_prime_UTR	Exon 17 of 17	NP_115484.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA6B	ENST00000586965.1	TSL:1	c.1967G>C	p.Arg656Pro	missense	Exon 17 of 17	ENSP00000465722.1	Q9H3T3-3
SEMA6B	ENST00000586582.6	TSL:1 MANE Select	c.*620G>C		3_prime_UTR	Exon 17 of 17	ENSP00000467290.1	Q9H3T3-1
SEMA6B	ENST00000676793.2		c.*620G>C		3_prime_UTR	Exon 17 of 17	ENSP00000503414.1	Q9H3T3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000734

AC:

AN:

136218

AF XY:

0.0000135

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000732

AC:

AN:

546638

Hom.:

Cov.:

AF XY:

0.00000676

AC XY:

AN XY:

295748

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15674

American (AMR)

AF:

0.00

AC:

AN:

34652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19952

East Asian (EAS)

AF:

0.00

AC:

AN:

32028

South Asian (SAS)

AF:

0.00

AC:

AN:

62618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2442

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

315408

Other (OTH)

AF:

0.00

AC:

AN:

30314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.8

(source)

DANN

Benign

0.84

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.35

M_CAP

Benign

0.020

MetaRNN

Benign

0.13

PhyloP100

-1.2

Sift4G

Pathogenic

0.0

Vest4

0.27

MVP

0.43

GERP RS

-3.9

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over