chr15-90219820-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_198925.4(SEMA4B):​c.412C>T​(p.Leu138Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. L138I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SEMA4B
NM_198925.4 missense

Scores

2
9
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13
Variant links:
Genes affected
SEMA4B (HGNC:10730): (semaphorin 4B) Predicted to enable chemorepellent activity and semaphorin receptor binding activity. Predicted to be involved in several processes, including generation of neurons; neural crest cell migration; and semaphorin-plexin signaling pathway. Predicted to be located in plasma membrane. Predicted to be active in extracellular space. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEMA4BNM_198925.4 linkc.412C>T p.Leu138Phe missense_variant Exon 4 of 14 ENST00000411539.7 NP_945119.1 Q9NPR2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEMA4BENST00000411539.7 linkc.412C>T p.Leu138Phe missense_variant Exon 4 of 14 1 NM_198925.4 ENSP00000394720.2 Q9NPR2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461234
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726944
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Uncertain
0.045
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.84
.;T
M_CAP
Benign
0.014
T
MetaRNN
Pathogenic
0.75
D;D
MetaSVM
Benign
-0.86
T
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-3.6
D;D
REVEL
Uncertain
0.31
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0060
D;D
Vest4
0.79
MVP
0.45
MPC
0.88
ClinPred
1.0
D
GERP RS
5.7
gMVP
0.95

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: rs1023994109; hg19: chr15-90763052; API