3-50269320-GC-G

Variant names:

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

Variant summary

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

The NM_001290061.1(SEMA3B):​c.86delC​(p.Pro29HisfsTer86) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000293 in 1,364,126 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SEMA3B NM_001290061.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290061.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3B	NM_001290060.2	MANE Select	c.86delC	p.Pro29HisfsTer86	frameshift	Exon 1 of 17	NP_001276989.1
	SEMA3B	NM_001290061.1		c.86delC	p.Pro29HisfsTer86	frameshift	Exon 1 of 17	NP_001276990.1
	SEMA3B	NM_001435956.1		c.86delC	p.Pro29HisfsTer86	frameshift	Exon 4 of 20	NP_001422885.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3B	ENST00000616701.5	TSL:1 MANE Select	c.86delC	p.Pro29HisfsTer86	frameshift	Exon 1 of 17	ENSP00000484146.1
	SEMA3B	ENST00000611067.4	TSL:1	c.86delC	p.Pro29HisfsTer86	frameshift	Exon 1 of 17	ENSP00000480680.1
	SEMA3B	ENST00000433753.4	TSL:1	c.86delC	p.Pro29HisfsTer86	frameshift	Exon 1 of 17	ENSP00000485281.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000293 AC: 4 AN: 1364126 Hom.: 0 Cov.: 30 AF XY: 0.00000297 AC XY: 2 AN XY: 672964

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.0000131 AC: 1 AN: 76168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39398

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

European-Non Finnish (NFE) AF: 0.00000280 AC: 3 AN: 1069888

Other (OTH) AF: 0.00 AC: 0 AN: 56572

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0547993), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;