19-4543825-C-T
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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.2443G>A(p.Asp815Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,214,464 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000088 ( 0 hom. )
Consequence
SEMA6B
NM_032108.4 missense
NM_032108.4 missense
Scores
2
1
13
Clinical Significance
Conservation
PhyloP100: 0.925
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=0.18631777).
BS2
?
High AC in GnomAdExome4 at 94 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA6B | NM_032108.4 | c.2443G>A | p.Asp815Asn | missense_variant | 17/17 | ENST00000586582.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA6B | ENST00000586582.6 | c.2443G>A | p.Asp815Asn | missense_variant | 17/17 | 1 | NM_032108.4 | P1 | |
SEMA6B | ENST00000586965.1 | c.1851+592G>A | intron_variant | 1 | |||||
SEMA6B | ENST00000676793.1 | c.2443G>A | p.Asp815Asn | missense_variant | 17/17 | P1 | |||
SEMA6B | ENST00000677828.1 | c.*1705G>A | 3_prime_UTR_variant, NMD_transcript_variant | 17/17 |
Frequencies
GnomAD3 genomes ? AF: 0.0000199 AC: 3AN: 150894Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000884 AC: 94AN: 1063570Hom.: 0 Cov.: 33 AF XY: 0.0000757 AC XY: 38AN XY: 502064
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GnomAD4 genome ? AF: 0.0000199 AC: 3AN: 150894Hom.: 0 Cov.: 32 AF XY: 0.0000407 AC XY: 3AN XY: 73702
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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 17, 2022 | The c.2443G>A (p.D815N) alteration is located in exon 17 (coding exon 16) of the SEMA6B gene. This alteration results from a G to A substitution at nucleotide position 2443, causing the aspartic acid (D) at amino acid position 815 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of loop (P = 0.0288);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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