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GeneBe

5-9044388-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_003966.3(SEMA5A):c.3090G>A(p.Ser1030=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000498 in 1,613,214 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

SEMA5A
NM_003966.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.18
Variant links:
Genes affected
SEMA5A (HGNC:10736): (semaphorin 5A) This gene belongs to the semaphorin gene family that encodes membrane proteins containing a semaphorin domain and several thrombospondin type-1 repeats. Members of this family are involved in axonal guidance during neural development. This gene has been implicated as an autism susceptibility gene.[provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-9044388-C-T is Benign according to our data. Variant chr5-9044388-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 734449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.18 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA5ANM_003966.3 linkuse as main transcriptc.3090G>A p.Ser1030= synonymous_variant 22/23 ENST00000382496.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA5AENST00000382496.10 linkuse as main transcriptc.3090G>A p.Ser1030= synonymous_variant 22/231 NM_003966.3 P1
ENST00000506519.1 linkuse as main transcriptn.669+1111C>T intron_variant, non_coding_transcript_variant 3
SEMA5AENST00000652226.1 linkuse as main transcriptc.3090G>A p.Ser1030= synonymous_variant 24/25 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000585
AC:
89
AN:
152080
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000676
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000434
AC:
109
AN:
251312
Hom.:
0
AF XY:
0.000405
AC XY:
55
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.000615
Gnomad AMR exome
AF:
0.000694
Gnomad ASJ exome
AF:
0.000496
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000519
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000489
AC:
714
AN:
1461018
Hom.:
0
Cov.:
31
AF XY:
0.000468
AC XY:
340
AN XY:
726814
show subpopulations
Gnomad4 AFR exome
AF:
0.000867
Gnomad4 AMR exome
AF:
0.000649
Gnomad4 ASJ exome
AF:
0.000344
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000543
Gnomad4 OTH exome
AF:
0.000530
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000591
AC:
90
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.000605
AC XY:
45
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.000506
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000676
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000391
Hom.:
0
Bravo
AF:
0.000555
EpiCase
AF:
0.000600
EpiControl
AF:
0.000771

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -
SEMA5A-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 05, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
0.41
Dann
Benign
0.84

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: rs150116452; hg19: chr5-9044500; API