3-52435690-G-C

Variant names:

• chr3-52435690-G-C
• NM_020163.3:c.2262C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020163.3(SEMA3G):​c.2262C>G​(p.Ser754Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SEMA3G NM_020163.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00300
• Publications: 0 publications found

Genes affected

SEMA3G (HGNC:30400): (semaphorin 3G) The transcription of this gene is activated by PPAR-gamma, and the resulting protein product plays a role in endothelial cell migration. Expression of this gene also inhibits tumor cell migration and invasion. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059064686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3G	NM_020163.3	c.2262C>G	p.Ser754Arg	missense_variant	Exon 16 of 16	ENST00000231721.7	NP_064548.1
SEMA3G	XM_024453642.2	c.2316C>G	p.Ser772Arg	missense_variant	Exon 17 of 17		XP_024309410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3G	ENST00000231721.7	c.2262C>G	p.Ser754Arg	missense_variant	Exon 16 of 16	1	NM_020163.3	ENSP00000231721.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2262C>G (p.S754R) alteration is located in exon 16 (coding exon 16) of the SEMA3G gene. This alteration results from a C to G substitution at nucleotide position 2262, causing the serine (S) at amino acid position 754 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.0030
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.13
Sift	Benign	0.26	T
Sift4G	Benign	0.59	T
Polyphen		0.0030	B
Vest4		0.17
MutPred		0.39		Gain of glycosylation at S754 (P = 0.0016);
MVP		0.85
MPC		0.24
ClinPred		0.058	T
GERP RS		1.9
Varity_R		0.077
gMVP		0.19
Mutation Taster		=91/9	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

hg19: chr3-52469706;