3-50269247-C-G

Variant names:

• chr3-50269247-C-G
• NM_001290060.2:c.7C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001290060.2(SEMA3B):​c.7C>G​(p.Arg3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SEMA3B NM_001290060.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20042121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3B	NM_001290060.2	c.7C>G	p.Arg3Gly	missense_variant	Exon 1 of 17	ENST00000616701.5	NP_001276989.1
SEMA3B	NM_001290061.1	c.7C>G	p.Arg3Gly	missense_variant	Exon 1 of 17		NP_001276990.1
SEMA3B	NM_004636.4	c.7C>G	p.Arg3Gly	missense_variant	Exon 2 of 18		NP_004627.1
SEMA3B	NM_001005914.3	c.7C>G	p.Arg3Gly	missense_variant	Exon 2 of 18		NP_001005914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3B	ENST00000616701.5	c.7C>G	p.Arg3Gly	missense_variant	Exon 1 of 17	1	NM_001290060.2	ENSP00000484146.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383584 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 682890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	18
DANN	Benign	0.64
DEOGEN2	Benign	0.058	.;T;T;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.74	T;T;.;T;T
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.63	T
Sift4G	Uncertain	0.042	D;D;D;D;D
Polyphen		0.18	.;B;B;.;.
Vest4		0.30, 0.28, 0.31, 0.38
MutPred		0.41		Loss of methylation at R3 (P = 0.0011);Loss of methylation at R3 (P = 0.0011);Loss of methylation at R3 (P = 0.0011);Loss of methylation at R3 (P = 0.0011);Loss of methylation at R3 (P = 0.0011);
MVP		0.36
ClinPred		0.49	T
GERP RS		-0.18
Varity_R		0.096
gMVP		0.62

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: chr3-50306679;