chr3-50269328-C-A

Variant names:

• chr3-50269328-C-A
• NM_001290060.2:c.88C>A

Variant summary

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

The NM_001290060.2(SEMA3B):​c.88C>A​(p.Arg30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,359,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000015 (0 hom.)
• Consequence: SEMA3B NM_001290060.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.759

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=0.25660324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3B	NM_001290060.2	c.88C>A	p.Arg30Ser	missense_variant	Exon 1 of 17	ENST00000616701.5	NP_001276989.1
SEMA3B	NM_001290061.1	c.88C>A	p.Arg30Ser	missense_variant	Exon 1 of 17		NP_001276990.1
SEMA3B	NM_004636.4	c.88C>A	p.Arg30Ser	missense_variant	Exon 2 of 18		NP_004627.1
SEMA3B	NM_001005914.3	c.88C>A	p.Arg30Ser	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.88C>A	p.Arg30Ser	missense_variant	Exon 1 of 17	1	NM_001290060.2	ENSP00000484146.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1359932 Hom.: 0 Cov.: 30 AF XY: 0.00000298 AC XY: 2 AN XY: 670518

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.37e-7

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	Pathogenic	0.86
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Benign	0.90
DEOGEN2	Benign	0.21	.;T;T;.;.
Eigen	Benign	0.073
Eigen_PC	Benign	0.0027
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.84	T;D;.;D;D
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-0.56	T
PrimateAI	Uncertain	0.66	T
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		0.99	.;D;D;.;.
Vest4		0.33, 0.29, 0.32, 0.43
MutPred		0.54		Loss of methylation at R30 (P = 0.0252);Loss of methylation at R30 (P = 0.0252);Loss of methylation at R30 (P = 0.0252);Loss of methylation at R30 (P = 0.0252);Loss of methylation at R30 (P = 0.0252);
MVP		0.33
ClinPred		0.85	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.21
gMVP		0.94

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: chr3-50306759;