19-4543701-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.2567C>T(p.Pro856Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000406 in 1,230,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P856H) has been classified as Uncertain significance.
Frequency
Consequence
NM_032108.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA6B | NM_032108.4 | c.2567C>T | p.Pro856Leu | missense_variant | 17/17 | ENST00000586582.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA6B | ENST00000586582.6 | c.2567C>T | p.Pro856Leu | missense_variant | 17/17 | 1 | NM_032108.4 | P1 | |
SEMA6B | ENST00000586965.1 | c.1852-605C>T | intron_variant | 1 | |||||
SEMA6B | ENST00000676793.1 | c.2567C>T | p.Pro856Leu | missense_variant | 17/17 | P1 | |||
SEMA6B | ENST00000677828.1 | c.*1829C>T | 3_prime_UTR_variant, NMD_transcript_variant | 17/17 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000278 AC: 3AN: 1077850Hom.: 0 Cov.: 32 AF XY: 0.00000196 AC XY: 1AN XY: 508930
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74460
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | The c.2567C>T (p.P856L) alteration is located in exon 17 (coding exon 16) of the SEMA6B gene. This alteration results from a C to T substitution at nucleotide position 2567, causing the proline (P) at amino acid position 856 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at