19-4543776-C-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_032108.4(SEMA6B):c.2492G>T(p.Arg831Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,222,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
SEMA6B
NM_032108.4 missense
NM_032108.4 missense
Scores
1
2
13
Clinical Significance
Conservation
PhyloP100: 1.21
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.121536136).
BS2
?
High AC in GnomAdExome4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA6B | NM_032108.4 | c.2492G>T | p.Arg831Met | missense_variant | 17/17 | ENST00000586582.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA6B | ENST00000586582.6 | c.2492G>T | p.Arg831Met | missense_variant | 17/17 | 1 | NM_032108.4 | P1 | |
SEMA6B | ENST00000586965.1 | c.1851+641G>T | intron_variant | 1 | |||||
SEMA6B | ENST00000676793.1 | c.2492G>T | p.Arg831Met | missense_variant | 17/17 | P1 | |||
SEMA6B | ENST00000677828.1 | c.*1754G>T | 3_prime_UTR_variant, NMD_transcript_variant | 17/17 |
Frequencies
GnomAD3 genomes ? AF: 0.00000665 AC: 1AN: 150424Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000112 AC: 12AN: 1071688Hom.: 0 Cov.: 32 AF XY: 0.00000988 AC XY: 5AN XY: 506032
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GnomAD4 genome ? AF: 0.00000665 AC: 1AN: 150424Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73482
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2023 | The c.2492G>T (p.R831M) alteration is located in exon 17 (coding exon 16) of the SEMA6B gene. This alteration results from a G to T substitution at nucleotide position 2492, causing the arginine (R) at amino acid position 831 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N;N;N
PrimateAI
Pathogenic
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of methylation at R831 (P = 0.0475);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at