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GeneBe

5-9044535-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003966.3(SEMA5A):c.2943C>T(p.Leu981=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,613,750 control chromosomes in the GnomAD database, including 398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 25 hom., cov: 32)
Exomes 𝑓: 0.019 ( 373 hom. )

Consequence

SEMA5A
NM_003966.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.372
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.69).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-9044535-G-A is Benign according to our data. Variant chr5-9044535-G-A is described in ClinVar as [Benign]. Clinvar id is 3059430.Status of the report is criteria_provided_single_submitter, 1 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=-0.372 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0143 (2183/152216) while in subpopulation NFE AF= 0.0207 (1405/68012). AF 95% confidence interval is 0.0198. There are 25 homozygotes in gnomad4. There are 977 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 25 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA5ANM_003966.3 linkuse as main transcriptc.2943C>T p.Leu981= synonymous_variant 22/23 ENST00000382496.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA5AENST00000382496.10 linkuse as main transcriptc.2943C>T p.Leu981= synonymous_variant 22/231 NM_003966.3 P1
ENST00000506519.1 linkuse as main transcriptn.669+1258G>A intron_variant, non_coding_transcript_variant 3
SEMA5AENST00000652226.1 linkuse as main transcriptc.2943C>T p.Leu981= synonymous_variant 24/25 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0144
AC:
2186
AN:
152098
Hom.:
25
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00910
Gnomad AMI
AF:
0.123
Gnomad AMR
AF:
0.00995
Gnomad ASJ
AF:
0.0138
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00208
Gnomad FIN
AF:
0.00604
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.0207
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.0117
AC:
2929
AN:
251350
Hom.:
27
AF XY:
0.0117
AC XY:
1596
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.00904
Gnomad AMR exome
AF:
0.00610
Gnomad ASJ exome
AF:
0.0111
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00333
Gnomad FIN exome
AF:
0.00679
Gnomad NFE exome
AF:
0.0188
Gnomad OTH exome
AF:
0.0121
GnomAD4 exome
AF:
0.0192
AC:
28115
AN:
1461534
Hom.:
373
Cov.:
32
AF XY:
0.0187
AC XY:
13564
AN XY:
727100
show subpopulations
Gnomad4 AFR exome
AF:
0.00878
Gnomad4 AMR exome
AF:
0.00601
Gnomad4 ASJ exome
AF:
0.0106
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00292
Gnomad4 FIN exome
AF:
0.00728
Gnomad4 NFE exome
AF:
0.0230
Gnomad4 OTH exome
AF:
0.0162
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0143
AC:
2183
AN:
152216
Hom.:
25
Cov.:
32
AF XY:
0.0131
AC XY:
977
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.00905
Gnomad4 AMR
AF:
0.00994
Gnomad4 ASJ
AF:
0.0138
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.00604
Gnomad4 NFE
AF:
0.0207
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.0145
Hom.:
9
Bravo
AF:
0.0145
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.0206
EpiControl
AF:
0.0193

ClinVar

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

Submissions by phenotype

SEMA5A-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMay 09, 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
-0.69
Cadd
Benign
7.5
Dann
Benign
0.88

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: rs11741172; hg19: chr5-9044647; COSMIC: COSV66795064; API