3-50269320-G-GC

Variant names:

• chr3-50269320-G-GC
• rs67324803
• NM_001290060.2:c.86dupC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001290060.2(SEMA3B):​c.86dupC​(p.Arg30ThrfsTer33) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEMA3B NM_001290060.2 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0550
• Publications: 10 publications found

Genes affected

SEMA3B (HGNC:10724): (semaphorin 3B) The protein encoded by this gene belongs to the class-3 semaphorin/collapsin family, whose members function in growth cone guidance during neuronal development. This family member inhibits axonal extension and has been shown to act as a tumor suppressor by inducing apoptosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

SEMA3B-AS1 (HGNC:49096): (SEMA3B antisense RNA 1 (head to head))

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-50269320-G-GC is Benign according to our data. Variant chr3-50269320-G-GC is described in ClinVar as Benign. ClinVar VariationId is 3060238.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3B	NM_001290060.2	c.86dupC	p.Arg30ThrfsTer33	frameshift_variant	Exon 1 of 17	ENST00000616701.5	NP_001276989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3B	ENST00000616701.5	c.86dupC	p.Arg30ThrfsTer33	frameshift_variant	Exon 1 of 17	1	NM_001290060.2	ENSP00000484146.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 1.00 AC: 111467 AN: 111490 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1364122 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 672962

African (AFR) AF: 0.00 AC: 0 AN: 29840

American (AMR) AF: 0.00 AC: 0 AN: 27942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23568

East Asian (EAS) AF: 0.00 AC: 0 AN: 35530

South Asian (SAS) AF: 0.00 AC: 0 AN: 76168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5220

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069882

Other (OTH) AF: 0.00 AC: 0 AN: 56570

GnomAD4 genome Cov.: 33

Alfa AF: 0.999 Hom.: 6703

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SEMA3B-related disorder Benign:1

Jun 17, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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
PhyloP100		-0.055

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs67324803; hg19: chr3-50306752; COSMIC: COSV60350820; COSMIC: COSV60350820;