rs372894044

Variant names:

• chr3-122910884-C-T
• rs372894044
• NM_001031702.4:c.3253G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001031702.4(SEMA5B):​c.3253G>A​(p.Gly1085Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000141 in 1,613,122 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 0.000072 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: SEMA5B NM_001031702.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.41
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.060780436).

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.3253G>A	p.Gly1085Arg	missense	Exon 22 of 23	NP_001026872.2	Q9P283-1
	SEMA5B	NM_001256347.1		c.3415G>A	p.Gly1139Arg	missense	Exon 22 of 23	NP_001243276.1	Q9P283-4
	SEMA5B	NM_001437563.1		c.3325G>A	p.Gly1109Arg	missense	Exon 22 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.3253G>A	p.Gly1085Arg	missense	Exon 22 of 23	ENSP00000350215.3	Q9P283-1
	SEMA5B	ENST00000451055.6	TSL:2	c.3415G>A	p.Gly1139Arg	missense	Exon 22 of 23	ENSP00000389588.2	Q9P283-4
	SEMA5B	ENST00000616742.4	TSL:5	c.3253G>A	p.Gly1085Arg	missense	Exon 22 of 23	ENSP00000479602.1	Q9P283-1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 151916 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000207 AC: 52 AN: 251366 AF XY: 0.000265

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000148 AC: 216 AN: 1461206 Hom.: 0 Cov.: 34 AF XY: 0.000197 AC XY: 143 AN XY: 726912

African (AFR) AF: 0.000120 AC: 4 AN: 33464

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00138 AC: 119 AN: 86228

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5286

European-Non Finnish (NFE) AF: 0.0000728 AC: 81 AN: 1111966

Other (OTH) AF: 0.000149 AC: 9 AN: 60324

GnomAD4 genome AF: 0.0000724 AC: 11 AN: 151916 Hom.: 0 Cov.: 31 AF XY: 0.0000944 AC XY: 7 AN XY: 74180

African (AFR) AF: 0.0000242 AC: 1 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000625 AC: 3 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.0000591 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000198 AC: 24

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	-0.38	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.4
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.083
Sift	Uncertain	0.010	D
Sift4G	Benign	0.081	T
Polyphen		0.90	P
Vest4		0.37
MutPred		0.33		Loss of ubiquitination at K1089 (P = 0.02)
MVP		0.62
MPC		0.93
ClinPred		0.14	T
GERP RS		4.9
Varity_R		0.10
gMVP		0.67
Mutation Taster		=85/15	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: rs372894044; hg19: chr3-122629731; COSMIC: COSV99531374;