5-116447034-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_020796.5(SEMA6A):​c.2672C>T​(p.Pro891Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000361 in 1,613,868 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P891Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00036 ( 4 hom. )

Consequence

SEMA6A
NM_020796.5 missense

Scores

1
8
9

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.26
Variant links:
Genes affected
SEMA6A (HGNC:10738): (semaphorin 6A) Predicted to enable identical protein binding activity; signaling receptor binding activity; and transmembrane signaling receptor activity. Involved in cellular response to vascular endothelial growth factor stimulus; negative regulation of cell adhesion involved in sprouting angiogenesis; and negative regulation of signal transduction. Predicted to be integral component of membrane. Predicted to be active in extracellular space. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.100030005).
BP6
Variant 5-116447034-G-A is Benign according to our data. Variant chr5-116447034-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 713698.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA6ANM_020796.5 linkuse as main transcriptc.2672C>T p.Pro891Leu missense_variant 19/19 ENST00000343348.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA6AENST00000343348.11 linkuse as main transcriptc.2672C>T p.Pro891Leu missense_variant 19/191 NM_020796.5 P4Q9H2E6-1

Frequencies

GnomAD3 genomes
AF:
0.000342
AC:
52
AN:
152056
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000412
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000454
AC:
113
AN:
249014
Hom.:
1
AF XY:
0.000518
AC XY:
70
AN XY:
135200
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000550
Gnomad ASJ exome
AF:
0.00279
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000443
Gnomad OTH exome
AF:
0.000826
GnomAD4 exome
AF:
0.000363
AC:
530
AN:
1461694
Hom.:
4
Cov.:
31
AF XY:
0.000385
AC XY:
280
AN XY:
727126
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000537
Gnomad4 ASJ exome
AF:
0.00222
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000371
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000330
Gnomad4 OTH exome
AF:
0.000613
GnomAD4 genome
AF:
0.000342
AC:
52
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.000323
AC XY:
24
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000653
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.000195
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000412
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000558
Hom.:
0
Bravo
AF:
0.000442
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000855
AC:
7
ExAC
AF:
0.000439
AC:
53
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000818
EpiControl
AF:
0.000593

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.19
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.091
.;T;T;.;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.96
.;D;D;D;.
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.10
T;T;T;T;T
MetaSVM
Benign
-0.50
T
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-5.0
D;D;D;D;D
REVEL
Benign
0.25
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D;D
Polyphen
1.0
.;.;D;D;.
Vest4
0.67
MVP
0.33
MPC
0.37
ClinPred
0.10
T
GERP RS
4.8
gMVP
0.54

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: rs185504747; hg19: chr5-115782730; COSMIC: COSV56711116; COSMIC: COSV56711116; API