NM_001031702.4:c.2665G>A

Variant names:

• chr3-122912903-C-T
• rs200481661
• NM_001031702.4:c.2665G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001031702.4(SEMA5B):​c.2665G>A​(p.Gly889Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000059 in 1,611,308 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: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: SEMA5B NM_001031702.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• Publications: 2 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17294374).

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.2665G>A	p.Gly889Ser	missense	Exon 18 of 23	NP_001026872.2	Q9P283-1
	SEMA5B	NM_001256347.1		c.2827G>A	p.Gly943Ser	missense	Exon 18 of 23	NP_001243276.1	Q9P283-4
	SEMA5B	NM_001437563.1		c.2737G>A	p.Gly913Ser	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.2665G>A	p.Gly889Ser	missense	Exon 18 of 23	ENSP00000350215.3	Q9P283-1
	SEMA5B	ENST00000451055.6	TSL:2	c.2827G>A	p.Gly943Ser	missense	Exon 18 of 23	ENSP00000389588.2	Q9P283-4
	SEMA5B	ENST00000616742.4	TSL:5	c.2665G>A	p.Gly889Ser	missense	Exon 18 of 23	ENSP00000479602.1	Q9P283-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000491 AC: 12 AN: 244538 AF XY: 0.0000451

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000681

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000624 AC: 91 AN: 1459000 Hom.: 0 Cov.: 31 AF XY: 0.0000606 AC XY: 44 AN XY: 725698

African (AFR) AF: 0.00 AC: 0 AN: 33254

American (AMR) AF: 0.00 AC: 0 AN: 44422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00229 AC: 90 AN: 39366

South Asian (SAS) AF: 0.00 AC: 0 AN: 85992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110830

Other (OTH) AF: 0.0000166 AC: 1 AN: 60230

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74480

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000577 AC: 7

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.18
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.38
Sift	Benign	0.058	T
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.53
MVP		0.87
MPC		0.89
ClinPred		0.62	D
GERP RS		5.2
Varity_R		0.66
gMVP		0.48
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs200481661; hg19: chr3-122631750; COSMIC: COSV52106846; COSMIC: COSV52106846;