7-83367661-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012431.3(SEMA3E):​c.2253T>G​(p.Tyr751*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

SEMA3E
NM_012431.3 stop_gained

Scores

2
1
4

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -1.27
Variant links:
Genes affected
SEMA3E (HGNC:10727): (semaphorin 3E) Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. This gene encodes a class 4 semaphorin. This gene encodes a class 3 semaphorin. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SEMA3ENM_012431.3 linkc.2253T>G p.Tyr751* stop_gained 17/17 ENST00000643230.2 NP_036563.1 O15041-1
SEMA3ENM_001178129.2 linkc.2073T>G p.Tyr691* stop_gained 17/17 NP_001171600.1 O15041-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SEMA3EENST00000643230.2 linkc.2253T>G p.Tyr751* stop_gained 17/17 NM_012431.3 ENSP00000496491.1 O15041-1
SEMA3EENST00000643441.1 linkn.2238T>G non_coding_transcript_exon_variant 17/17

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SEMA3E-related disorder Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesNov 17, 2023The SEMA3E c.2253T>G variant is predicted to result in premature protein termination (p.Tyr751*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is located near the end of the terminal exon of the SEMA3E gene, and early termination changes are also well tolerated in this gene overall. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
30
DANN
Uncertain
0.98
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.10
N
Vest4
0.58
GERP RS
-5.0

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-82996977; COSMIC: COSV57108139; COSMIC: COSV57108139; API