chr3-50269247-C-G

Variant names:

• chr3-50269247-C-G
• rs782185211
• NM_001290060.2:c.7C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 9/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3Q) has been classified as Uncertain significance.

• 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
• 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 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290060.2. 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.7C>G	p.Arg3Gly	missense	Exon 1 of 17	NP_001276989.1	Q13214-1
	SEMA3B	NM_001290061.1		c.7C>G	p.Arg3Gly	missense	Exon 1 of 17	NP_001276990.1	Q13214
	SEMA3B	NM_001435956.1		c.7C>G	p.Arg3Gly	missense	Exon 4 of 20	NP_001422885.1	Q13214-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3B	ENST00000616701.5	TSL:1 MANE Select	c.7C>G	p.Arg3Gly	missense	Exon 1 of 17	ENSP00000484146.1	Q13214-1
	SEMA3B	ENST00000611067.4	TSL:1	c.7C>G	p.Arg3Gly	missense	Exon 1 of 17	ENSP00000480680.1	A0A0C4DGV8
	SEMA3B	ENST00000433753.4	TSL:1	c.7C>G	p.Arg3Gly	missense	Exon 1 of 17	ENSP00000485281.1	Q13214-2

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

African (AFR) AF: 0.00 AC: 0 AN: 31558

American (AMR) AF: 0.00 AC: 0 AN: 35668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25142

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5598

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078136

Other (OTH) AF: 0.00 AC: 0 AN: 57828

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.20
PrimateAI	Uncertain	0.63	T
Sift4G	Uncertain	0.042	D
Polyphen		0.18	B
Vest4		0.30
MutPred		0.41		Loss of methylation at R3 (P = 0.0011)
MVP		0.36
ClinPred		0.49	T
GERP RS		-0.18
PromoterAI		-0.10	Neutral
Varity_R		0.096
gMVP		0.62
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs782185211; hg19: chr3-50306679;