NM_001290060.2:c.1244C>A

Variant names:

• chr3-50274469-C-A
• rs2071203
• NM_001290060.2:c.1244C>A

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.1244C>A​(p.Thr415Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 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. T415I) has been classified as Benign.

• 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: 1.85
• Publications: 21 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=0.08489624).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3B	NM_001290060.2	MANE Select	c.1244C>A	p.Thr415Asn	missense	Exon 11 of 17	NP_001276989.1
	SEMA3B	NM_001290061.1		c.1259C>A	p.Thr420Asn	missense	Exon 11 of 17	NP_001276990.1
	SEMA3B	NM_001435956.1		c.1244C>A	p.Thr415Asn	missense	Exon 14 of 20	NP_001422885.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3B	ENST00000616701.5	TSL:1 MANE Select	c.1244C>A	p.Thr415Asn	missense	Exon 11 of 17	ENSP00000484146.1
	SEMA3B	ENST00000611067.4	TSL:1	c.1259C>A	p.Thr420Asn	missense	Exon 11 of 17	ENSP00000480680.1
	SEMA3B	ENST00000433753.4	TSL:1	c.1241C>A	p.Thr414Asn	missense	Exon 11 of 17	ENSP00000485281.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397960 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690542

African (AFR) AF: 0.00 AC: 0 AN: 31134

American (AMR) AF: 0.00 AC: 0 AN: 33484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22104

East Asian (EAS) AF: 0.00 AC: 0 AN: 38586

South Asian (SAS) AF: 0.00 AC: 0 AN: 75320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5452

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082786

Other (OTH) AF: 0.00 AC: 0 AN: 57572

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.98	T
PhyloP100		1.8
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.16	T
Polyphen		0.0070	B
Vest4		0.047
MutPred		0.57		Loss of phosphorylation at T415 (P = 0.0497)
MVP		0.18
ClinPred		0.28	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.34
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2071203; hg19: chr3-50311900;