NM_017514.5:c.105C>G

Variant names:

• chrX-154460288-C-G
• rs1557203239
• NM_017514.5:c.105C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017514.5(PLXNA3):​c.105C>G​(p.His35Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 112,407 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 25)
• Consequence: PLXNA3 NM_017514.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.79
• Publications: 0 publications found

Genes affected

PLXNA3 (HGNC:9101): (plexin A3) This gene encodes a member of the plexin class of proteins. The encoded protein is a class 3 semaphorin receptor, and may be involved in cytoskeletal remodeling and as well as apoptosis. Studies of a similar gene in zebrafish suggest that it is important for axon pathfinding in the developing nervous system. This gene may be associated with tumor progression. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017514.5. 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
	PLXNA3	NM_017514.5	MANE Select	c.105C>G	p.His35Gln	missense	Exon 2 of 33	NP_059984.3	P51805

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA3	ENST00000369682.4	TSL:1 MANE Select	c.105C>G	p.His35Gln	missense	Exon 2 of 33	ENSP00000358696.3	P51805
	PLXNA3	ENST00000937806.1		c.105C>G	p.His35Gln	missense	Exon 2 of 33	ENSP00000607865.1
	PLXNA3	ENST00000955276.1		c.105C>G	p.His35Gln	missense	Exon 2 of 33	ENSP00000625335.1

Frequencies

GnomAD3 genomes AF: 0.00000890 AC: 1 AN: 112407 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000890 AC: 1 AN: 112407 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 34563

African (AFR) AF: 0.00 AC: 0 AN: 30938

American (AMR) AF: 0.00 AC: 0 AN: 10740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3579

South Asian (SAS) AF: 0.00 AC: 0 AN: 2747

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6211

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53120

Other (OTH) AF: 0.00 AC: 0 AN: 1498

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	PLXNA3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.0062	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.97
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-1.1	T
PhyloP100		2.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Vest4		0.75
MutPred		0.47		Loss of sheet (P = 0.0817)
MVP		0.85
ClinPred		0.98	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.62
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1557203239; hg19: chrX-153688628;