rs1043167831

Variant names:

• chrX-154460226-G-C
• rs1043167831
• NM_017514.5:c.43G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-154460226-G-C
• chrX-154460226-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017514.5(PLXNA3):​c.43G>C​(p.Gly15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,207,909 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G15G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: PLXNA3 NM_017514.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 2.82
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2821439).

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.43G>C	p.Gly15Arg	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.43G>C	p.Gly15Arg	missense	Exon 2 of 33	ENSP00000358696.3	P51805
	PLXNA3	ENST00000937806.1		c.43G>C	p.Gly15Arg	missense	Exon 2 of 33	ENSP00000607865.1
	PLXNA3	ENST00000955276.1		c.43G>C	p.Gly15Arg	missense	Exon 2 of 33	ENSP00000625335.1

Frequencies

GnomAD3 genomes AF: 0.00000890 AC: 1 AN: 112400 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000323

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1095509 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 361667

African (AFR) AF: 0.0000759 AC: 2 AN: 26365

American (AMR) AF: 0.00 AC: 0 AN: 35176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19339

East Asian (EAS) AF: 0.00 AC: 0 AN: 30194

South Asian (SAS) AF: 0.00 AC: 0 AN: 54082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3945

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840848

Other (OTH) AF: 0.00 AC: 0 AN: 46006

GnomAD4 genome AF: 0.00000890 AC: 1 AN: 112400 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 34572

African (AFR) AF: 0.0000323 AC: 1 AN: 30928

American (AMR) AF: 0.00 AC: 0 AN: 10758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3576

South Asian (SAS) AF: 0.00 AC: 0 AN: 2743

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53101

Other (OTH) AF: 0.00 AC: 0 AN: 1502

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)
-	1	-	PLXNA3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	21
DANN	Uncertain	0.97
FATHMM_MKL	Benign	0.51	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.89	T
PhyloP100		2.8
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.17
Sift	Benign	0.19	T
Sift4G	Benign	0.55	T
Vest4		0.37
MutPred		0.70		Gain of methylation at G15 (P = 0.015)
MVP		0.17
ClinPred		0.24	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.52
Mutation Taster		=92/8	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: rs1043167831; hg19: chrX-153688566;