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GeneBe

5-9051901-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003966.3(SEMA5A):c.2817G>A(p.Pro939=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,166 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 24 hom. )

Consequence

SEMA5A
NM_003966.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.42
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 -21 ACMG points.

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=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-9051901-C-T is Benign according to our data. Variant chr5-9051901-C-T is described in ClinVar as [Benign]. Clinvar id is 733345.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=-4.42 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00102 (155/152296) while in subpopulation SAS AF= 0.0197 (95/4818). AF 95% confidence interval is 0.0165. There are 3 homozygotes in gnomad4. There are 95 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA5ANM_003966.3 linkuse as main transcriptc.2817G>A p.Pro939= synonymous_variant 20/23 ENST00000382496.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA5AENST00000382496.10 linkuse as main transcriptc.2817G>A p.Pro939= synonymous_variant 20/231 NM_003966.3 P1
SEMA5AENST00000652226.1 linkuse as main transcriptc.2817G>A p.Pro939= synonymous_variant 22/25 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00102
AC:
155
AN:
152178
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00128
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0197
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00210
AC:
528
AN:
251386
Hom.:
8
AF XY:
0.00273
AC XY:
371
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.00129
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0160
Gnomad FIN exome
AF:
0.000231
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.00103
AC:
1503
AN:
1461870
Hom.:
24
Cov.:
31
AF XY:
0.00143
AC XY:
1039
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00137
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0155
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.0000306
Gnomad4 OTH exome
AF:
0.00106
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00102
AC:
155
AN:
152296
Hom.:
3
Cov.:
32
AF XY:
0.00128
AC XY:
95
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00127
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0197
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000220
Hom.:
0
Bravo
AF:
0.000552
Asia WGS
AF:
0.0140
AC:
49
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -
SEMA5A-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 02, 2019This variant is classified as 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
-0.89
Cadd
Benign
0.24
Dann
Benign
0.92

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: rs145965659; hg19: chr5-9052013; COSMIC: COSV101227897; COSMIC: COSV101227897; API