3-122911499-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001031702.4(SEMA5B):c.3083A>G(p.Asp1028Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,607,440 control chromosomes in the GnomAD database, including 505,592 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.71 (40100 hom., cov: 33)
  • Exomes 𝑓: 0.79 (465492 hom.)
• Consequence: SEMA5B NM_001031702.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4301991E-6).
• BP6: Variant 3-122911499-T-C is Benign according to our data. Variant chr3-122911499-T-C is described in ClinVar as [Benign]. Clinvar id is 1230603.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5B	NM_001031702.4	c.3083A>G	p.Asp1028Gly	missense_variant	21/23	ENST00000357599.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA5B	ENST00000357599.8	c.3083A>G	p.Asp1028Gly	missense_variant	21/23	1	NM_001031702.4

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108438 AN: 151656 Hom.: 40087 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.742

GnomAD3 exomes AF: 0.709 AC: 169644 AN: 239390 Hom.: 63050 AF XY: 0.723 AC XY: 93153 AN XY: 128830

Gnomad AFR exome AF: 0.577

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.781

Gnomad EAS exome AF: 0.331

Gnomad SAS exome AF: 0.731

Gnomad FIN exome AF: 0.728

Gnomad NFE exome AF: 0.829

Gnomad OTH exome AF: 0.750

GnomAD4 exome AF: 0.792 AC: 1152565 AN: 1455666 Hom.: 465492 Cov.: 52 AF XY: 0.792 AC XY: 572558 AN XY: 723298

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.530

Gnomad4 ASJ exome AF: 0.788

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.734

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.834

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.715 AC: 108491 AN: 151774 Hom.: 40100 Cov.: 33 AF XY: 0.709 AC XY: 52531 AN XY: 74136

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.743

Alfa AF: 0.798 Hom.: 98012

Bravo AF: 0.696

TwinsUK AF: 0.834 AC: 3093

ALSPAC AF: 0.835 AC: 3219

ESP6500AA AF: 0.579 AC: 2552

ESP6500EA AF: 0.832 AC: 7153

ExAC AF: 0.713 AC: 85587

Asia WGS AF: 0.588 AC: 2048 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	12
Dann	Benign	0.30
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.068	T;T;T;T;.;T;T
MetaRNN	Benign	0.0000014	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.27	T
Polyphen		0.0	.;.;B;.;B;.;.
Vest4		0.071, 0.099, 0.12, 0.14
MPC		0.35
ClinPred		0.0011	T
GERP RS		3.2
Varity_R		0.056
gMVP		0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs2303983; hg19: chr3-122630346; COSMIC: COSV52094192;