rs1407668886

Variant names:

• chr3-122910291-T-C
• rs1407668886
• NM_001031702.4:c.3308A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031702.4(SEMA5B):​c.3308A>G​(p.Lys1103Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SEMA5B NM_001031702.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• Publications: 0 publications found

Genes affected

SEMA5B (HGNC:10737): (semaphorin 5B) This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31326807).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031702.4. 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
	SEMA5B	NM_001031702.4	MANE Select	c.3308A>G	p.Lys1103Arg	missense	Exon 23 of 23	NP_001026872.2	Q9P283-1
	SEMA5B	NM_001256347.1		c.3470A>G	p.Lys1157Arg	missense	Exon 23 of 23	NP_001243276.1	Q9P283-4
	SEMA5B	NM_001437563.1		c.3380A>G	p.Lys1127Arg	missense	Exon 23 of 23	NP_001424492.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5B	ENST00000357599.8	TSL:1 MANE Select	c.3308A>G	p.Lys1103Arg	missense	Exon 23 of 23	ENSP00000350215.3	Q9P283-1
	SEMA5B	ENST00000451055.6	TSL:2	c.3470A>G	p.Lys1157Arg	missense	Exon 23 of 23	ENSP00000389588.2	Q9P283-4
	SEMA5B	ENST00000616742.4	TSL:5	c.3308A>G	p.Lys1103Arg	missense	Exon 23 of 23	ENSP00000479602.1	Q9P283-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248882 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461800 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727198

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Benign	0.043	D
Sift4G	Uncertain	0.036	D
Polyphen		0.93	P
Vest4		0.61
MutPred		0.25		Loss of ubiquitination at K1103 (P = 0.0134)
MVP		0.66
MPC		0.69
ClinPred		0.85	D
GERP RS		4.9
Varity_R		0.25
gMVP		0.68
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1407668886; hg19: chr3-122629138;