rs200617248

Variant names:

• chrX-154460238-G-A
• rs200617248
• NM_017514.5:c.55G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017514.5(PLXNA3):​c.55G>A​(p.Gly19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,208,510 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 50 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G19D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.00015 (0 hom. 50 hem.)
• Consequence: PLXNA3 NM_017514.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 1.18
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05299416).
• BS2: High Hemizygotes in GnomAdExome4 at 50 gene

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.55G>A	p.Gly19Ser	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.55G>A	p.Gly19Ser	missense	Exon 2 of 33	ENSP00000358696.3	P51805
	PLXNA3	ENST00000937806.1		c.55G>A	p.Gly19Ser	missense	Exon 2 of 33	ENSP00000607865.1
	PLXNA3	ENST00000955276.1		c.55G>A	p.Gly19Ser	missense	Exon 2 of 33	ENSP00000625335.1

Frequencies

GnomAD3 genomes AF: 0.0000801 AC: 9 AN: 112420 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000647

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000929

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: 0.000113

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000778 AC: 14 AN: 179866 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000733

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000153 AC: 168 AN: 1096036 Hom.: 0 Cov.: 31 AF XY: 0.000138 AC XY: 50 AN XY: 362078

African (AFR) AF: 0.0000379 AC: 1 AN: 26361

American (AMR) AF: 0.00 AC: 0 AN: 35179

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19365

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00 AC: 0 AN: 54106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3984

European-Non Finnish (NFE) AF: 0.000193 AC: 162 AN: 841198

Other (OTH) AF: 0.000109 AC: 5 AN: 46020

GnomAD4 genome AF: 0.0000800 AC: 9 AN: 112474 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 34650

African (AFR) AF: 0.0000645 AC: 2 AN: 31004

American (AMR) AF: 0.0000928 AC: 1 AN: 10779

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3559

South Asian (SAS) AF: 0.00 AC: 0 AN: 2727

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53122

Other (OTH) AF: 0.00 AC: 0 AN: 1518

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	0.090
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	17
DANN	Uncertain	0.97
FATHMM_MKL	Benign	0.66	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.94	T
PhyloP100		1.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.17
Sift	Benign	0.57	T
Sift4G	Benign	0.93	T
Vest4		0.18
MVP		0.56
ClinPred		0.019	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.39
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200617248; hg19: chrX-153688578;