X-154460379-C-T

Position:

• chrX-154460379-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_017514.5(PLXNA3):​c.196C>T​(p.His66Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,095,393 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.000014 (0 hom. 8 hem.)
• Consequence: PLXNA3 NM_017514.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.89

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21039847).
• BS2: High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA3	NM_017514.5	c.196C>T	p.His66Tyr	missense_variant	2/33	ENST00000369682.4
PLXNA3	XM_047442247.1	c.196C>T	p.His66Tyr	missense_variant	2/22
PLXNA3	XR_007068193.1	n.371C>T		non_coding_transcript_exon_variant	2/32
PLXNA3	XR_430556.4	n.371C>T		non_coding_transcript_exon_variant	2/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA3	ENST00000369682.4	c.196C>T	p.His66Tyr	missense_variant	2/33	1	NM_017514.5	P1
PLXNA3	ENST00000495040.1	n.146-720C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD3 exomes AF: 0.0000511 AC: 9 AN: 176140 Hom.: 0 AF XY: 0.0000952 AC XY: 6 AN XY: 63006

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000586

Gnomad SAS exome AF: 0.0000540

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 15 AN: 1095393 Hom.: 0 Cov.: 31 AF XY: 0.0000221 AC XY: 8 AN XY: 361357

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000398

Gnomad4 SAS exome AF: 0.0000371

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

Bravo AF: 0.0000416

ExAC AF: 0.0000577 AC: 7

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

PLXNA3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	1.0
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.2	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.027	D
Sift4G	Benign	0.092	T
Vest4		0.26
MutPred		0.50		Gain of phosphorylation at H66 (P = 0.0635);
MVP		0.55
ClinPred		0.28	T
GERP RS		4.8
gMVP		0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs782118070; hg19: chrX-153688719;