19-4542981-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000586965.1(SEMA6B):​c.1967G>A​(p.Arg656His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 698,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

SEMA6B
ENST00000586965.1 missense

Scores

1
8

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.21
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06393045).
BP6
Variant 19-4542981-C-T is Benign according to our data. Variant chr19-4542981-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388618.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEMA6BNM_032108.4 linkc.*620G>A 3_prime_UTR_variant Exon 17 of 17 ENST00000586582.6 NP_115484.2 Q9H3T3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEMA6BENST00000586582 linkc.*620G>A 3_prime_UTR_variant Exon 17 of 17 1 NM_032108.4 ENSP00000467290.1 Q9H3T3-1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152104
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000587
AC:
8
AN:
136218
Hom.:
0
AF XY:
0.0000541
AC XY:
4
AN XY:
73942
show subpopulations
Gnomad AFR exome
AF:
0.000155
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000122
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000110
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000659
AC:
36
AN:
546638
Hom.:
0
Cov.:
0
AF XY:
0.0000473
AC XY:
14
AN XY:
295748
show subpopulations
Gnomad4 AFR exome
AF:
0.0000638
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000501
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000919
Gnomad4 OTH exome
AF:
0.000165
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152104
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000869

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Oct 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

SEMA6B: BS1 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
6.4
DANN
Benign
0.89
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.064
T
Sift4G
Pathogenic
0.0
D
Vest4
0.088
MVP
0.33
GERP RS
-3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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: rs983460534; hg19: chr19-4542993; API