3-122912986-G-C

Variant names:

• chr3-122912986-G-C
• rs777097346
• NM_001031702.4:c.2582C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001031702.4(SEMA5B):​c.2582C>G​(p.Pro861Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,457,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P861L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SEMA5B NM_001031702.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27564448).

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.2582C>G	p.Pro861Arg	missense	Exon 18 of 23	NP_001026872.2	Q9P283-1
	SEMA5B	NM_001256347.1		c.2744C>G	p.Pro915Arg	missense	Exon 18 of 23	NP_001243276.1	Q9P283-4
	SEMA5B	NM_001437563.1		c.2654C>G	p.Pro885Arg	missense	Exon 18 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.2582C>G	p.Pro861Arg	missense	Exon 18 of 23	ENSP00000350215.3	Q9P283-1
	SEMA5B	ENST00000451055.6	TSL:2	c.2744C>G	p.Pro915Arg	missense	Exon 18 of 23	ENSP00000389588.2	Q9P283-4
	SEMA5B	ENST00000616742.4	TSL:5	c.2582C>G	p.Pro861Arg	missense	Exon 18 of 23	ENSP00000479602.1	Q9P283-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000302 AC: 7 AN: 232130 AF XY: 0.0000548

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000297

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: 0.0000165 AC: 24 AN: 1457410 Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22 AN XY: 724936

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.0000226 AC: 1 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25930

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.000244 AC: 21 AN: 85966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110306

Other (OTH) AF: 0.0000166 AC: 1 AN: 60084

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000251 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.033
Eigen_PC	Benign	-0.035
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.9
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.20
Sift	Uncertain	0.025	D
Sift4G	Benign	0.11	T
Polyphen		0.94	P
Vest4		0.43
MutPred		0.58		Gain of MoRF binding (P = 3e-04)
MVP		0.87
MPC		0.54
ClinPred		0.30	T
GERP RS		3.2
Varity_R		0.17
gMVP		0.27
Mutation Taster		=96/4	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: rs777097346; hg19: chr3-122631833;