chr3-50270936-C-T

Position:

• chr3-50270936-C-T

Variant summary

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

The NM_001290060.2(SEMA3B):​c.377C>T​(p.Thr126Ile) variant causes a missense 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEMA3B NM_001290060.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.32

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3B	NM_001290060.2	c.377C>T	p.Thr126Ile	missense_variant	4/17	ENST00000616701.5	NP_001276989.1
SEMA3B	NM_001290061.1	c.377C>T	p.Thr126Ile	missense_variant	4/17		NP_001276990.1
SEMA3B	NM_004636.4	c.377C>T	p.Thr126Ile	missense_variant	5/18		NP_004627.1
SEMA3B	NM_001005914.3	c.377C>T	p.Thr126Ile	missense_variant	5/18		NP_001005914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3B	ENST00000616701.5	c.377C>T	p.Thr126Ile	missense_variant	4/17	1	NM_001290060.2	ENSP00000484146	P5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.377C>T (p.T126I) alteration is located in exon 5 (coding exon 4) of the SEMA3B gene. This alteration results from a C to T substitution at nucleotide position 377, causing the threonine (T) at amino acid position 126 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Benign	0.87
DEOGEN2	Benign	0.29	.;T;T;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.94	D;D;.;D;D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Uncertain	0.00050	D
PrimateAI	Uncertain	0.68	T
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		1.0, 1.0	.;D;D;D;.
Vest4		0.63, 0.63, 0.64, 0.62
MutPred		0.74		Loss of catalytic residue at T126 (P = 0.0711);Loss of catalytic residue at T126 (P = 0.0711);Loss of catalytic residue at T126 (P = 0.0711);Loss of catalytic residue at T126 (P = 0.0711);Loss of catalytic residue at T126 (P = 0.0711);
MVP		0.47
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.89

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: chr3-50308367;