NM_017514.5:c.79G>T

Variant names:

• chrX-154460262-G-T
• rs149048914
• NM_017514.5:c.79G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017514.5(PLXNA3):​c.79G>T​(p.Val27Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,095,858 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: PLXNA3 NM_017514.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06637666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA3	NM_017514.5	c.79G>T	p.Val27Leu	missense_variant	Exon 2 of 33	ENST00000369682.4	NP_059984.3
PLXNA3	XM_047442247.1	c.79G>T	p.Val27Leu	missense_variant	Exon 2 of 22		XP_047298203.1
PLXNA3	XR_007068193.1	n.254G>T		non_coding_transcript_exon_variant	Exon 2 of 32
PLXNA3	XR_430556.4	n.254G>T		non_coding_transcript_exon_variant	Exon 2 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA3	ENST00000369682.4	c.79G>T	p.Val27Leu	missense_variant	Exon 2 of 33	1	NM_017514.5	ENSP00000358696.3
PLXNA3	ENST00000495040.1	n.146-837G>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1095858 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 361764

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.2
DANN	Benign	0.75
FATHMM_MKL	Benign	0.053	N
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.91	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.021
Sift	Benign	0.56	T
Sift4G	Benign	0.65	T
Vest4		0.084
MutPred		0.39		Loss of sheet (P = 0.1158);
MVP		0.10
ClinPred		0.039	T
GERP RS		-0.62
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs149048914; hg19: chrX-153688602;