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GeneBe

19-4543972-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032108.4(SEMA6B):c.2296G>A(p.Gly766Arg) 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. 12/19 in silico tools predict 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

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07787117).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA6BNM_032108.4 linkuse as main transcriptc.2296G>A p.Gly766Arg missense_variant 17/17 ENST00000586582.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA6BENST00000586582.6 linkuse as main transcriptc.2296G>A p.Gly766Arg missense_variant 17/171 NM_032108.4 P1Q9H3T3-1
SEMA6BENST00000586965.1 linkuse as main transcriptc.1851+445G>A intron_variant 1 Q9H3T3-3
SEMA6BENST00000676793.1 linkuse as main transcriptc.2296G>A p.Gly766Arg missense_variant 17/17 P1Q9H3T3-1
SEMA6BENST00000677828.1 linkuse as main transcriptc.*1558G>A 3_prime_UTR_variant, NMD_transcript_variant 17/17

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1052396
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
496800
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2022SEMA6B: PM2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
Cadd
Benign
9.1
Dann
Benign
0.93
DEOGEN2
Benign
0.11
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.57
T
M_CAP
Benign
0.080
D
MetaRNN
Benign
0.078
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Pathogenic
0.86
D
Sift4G
Benign
0.20
T
Polyphen
0.0010
B
Vest4
0.23
MutPred
0.14
Gain of methylation at G766 (P = 0.0374);
MVP
0.043
MPC
2.2
ClinPred
0.090
T
GERP RS
1.9
Varity_R
0.085
gMVP
0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4543984; API