Menu
GeneBe

19-4543963-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032108.4(SEMA6B):c.2305A>C(p.Thr769Pro) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SEMA6B
NM_032108.4 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0660
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.053625375).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA6BNM_032108.4 linkuse as main transcriptc.2305A>C p.Thr769Pro missense_variant 17/17 ENST00000586582.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA6BENST00000586582.6 linkuse as main transcriptc.2305A>C p.Thr769Pro missense_variant 17/171 NM_032108.4 P1Q9H3T3-1
SEMA6BENST00000586965.1 linkuse as main transcriptc.1851+454A>C intron_variant 1 Q9H3T3-3
SEMA6BENST00000676793.1 linkuse as main transcriptc.2305A>C p.Thr769Pro missense_variant 17/17 P1Q9H3T3-1
SEMA6BENST00000677828.1 linkuse as main transcriptc.*1567A>C 3_prime_UTR_variant, NMD_transcript_variant 17/17

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsSep 14, 2021The c.2305A>C (p.T769P) alteration is located in exon 17 (coding exon 16) of the SEMA6B gene. This alteration results from a A to C substitution at nucleotide position 2305, causing the threonine (T) at amino acid position 769 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.047
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
Cadd
Benign
3.4
Dann
Benign
0.41
DEOGEN2
Benign
0.059
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.26
T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.054
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Pathogenic
0.84
D
Sift4G
Benign
0.37
T
Polyphen
0.0
B
Vest4
0.084
MutPred
0.19
Loss of phosphorylation at T769 (P = 0.0026);
MVP
0.043
MPC
2.1
ClinPred
0.049
T
GERP RS
0.12
Varity_R
0.084
gMVP
0.26

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: rs966035437; hg19: chr19-4543975; COSMIC: COSV56703409; COSMIC: COSV56703409; API