19-4543611-G-A

Variant summary

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

The NM_032108.4(SEMA6B):​c.2657C>T​(p.Pro886Leu) 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

2
2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17
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]

Genome browser will be placed here

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=0.1974766).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEMA6BNM_032108.4 linkc.2657C>T p.Pro886Leu missense_variant Exon 17 of 17 ENST00000586582.6 NP_115484.2 Q9H3T3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEMA6BENST00000586582.6 linkc.2657C>T p.Pro886Leu missense_variant Exon 17 of 17 1 NM_032108.4 ENSP00000467290.1 Q9H3T3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1082650
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
511962
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
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Jul 11, 2024
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.053
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.65
T
M_CAP
Pathogenic
0.73
D
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Pathogenic
0.86
D
Sift4G
Uncertain
0.020
D
Polyphen
0.26
B
Vest4
0.24
MutPred
0.20
Gain of stability (P = 0.0053);
MVP
0.043
MPC
2.6
ClinPred
0.87
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.28
gMVP
0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1049242845; hg19: chr19-4543623; API