X-154467904-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_017514.5(PLXNA3):c.3723C>G(p.Ala1241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (20856 hom., 22396 hem., cov: 23)
  • Exomes 𝑓: 0.83 (263980 hom. 299405 hem.)
  • Failed GnomAD Quality Control
• Consequence: PLXNA3 NM_017514.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant X-154467904-C-G is Benign according to our data. Variant chrX-154467904-C-G is described in ClinVar as [Benign]. Clinvar id is 769207.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.25 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 20857 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA3	NM_017514.5	c.3723C>G	p.Ala1241=	synonymous_variant	21/33	ENST00000369682.4
PLXNA3	XM_047442247.1	c.3565C>G	p.Leu1189Val	missense_variant	21/22
PLXNA3	XR_007068193.1	n.3898C>G		non_coding_transcript_exon_variant	21/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA3	ENST00000369682.4	c.3723C>G	p.Ala1241=	synonymous_variant	21/33	1	NM_017514.5	P1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 75133 AN: 110553 Hom.: 20857 Cov.: 23 AF XY: 0.682 AC XY: 22361 AN XY: 32799

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.678

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.835 AC: 915391 AN: 1096729 Hom.: 263980 Cov.: 53 AF XY: 0.825 AC XY: 299405 AN XY: 362733

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.902

Gnomad4 ASJ exome AF: 0.704

Gnomad4 EAS exome AF: 0.903

Gnomad4 SAS exome AF: 0.567

Gnomad4 FIN exome AF: 0.895

Gnomad4 NFE exome AF: 0.870

Gnomad4 OTH exome AF: 0.784

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.680 AC: 75162 AN: 110609 Hom.: 20856 Cov.: 23 AF XY: 0.681 AC XY: 22396 AN XY: 32865

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.897

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.682

Alfa AF: 0.760 Hom.: 9557

Bravo AF: 0.666

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	8.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5987266; hg19: chrX-153696247;