rs61636768

Variant names:

• chr7-83392656-A-C
• rs61636768
• NM_012431.3:c.1566T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-83392656-A-C
• chr7-83392656-A-G

Variant summary

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

The NM_012431.3(SEMA3E):​c.1566T>G​(p.Tyr522*) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y522Y) has been classified as Benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SEMA3E NM_012431.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666

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]

ACMG classification

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 rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.1566T>G	p.Tyr522*	stop_gained	Exon 14 of 17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2	c.1386T>G	p.Tyr462*	stop_gained	Exon 14 of 17		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2	c.1566T>G	p.Tyr522*	stop_gained	Exon 14 of 17		NM_012431.3	ENSP00000496491.1
SEMA3E	ENST00000642232.1	c.1566T>G	p.Tyr522*	stop_gained	Exon 14 of 17			ENSP00000494064.1
SEMA3E	ENST00000643441.1	n.1551T>G		non_coding_transcript_exon_variant	Exon 14 of 17

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.27	N
Vest4		0.92
GERP RS		-6.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs61636768; hg19: chr7-83021972;