7-132133146-G-C

Position:

• chr7-132133146-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020911.2(PLXNA4):​c.5492C>G​(p.Ala1831Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1831T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLXNA4 NM_020911.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.96

Genes affected

PLXNA4 (HGNC:9102): (plexin A4) Predicted to enable semaphorin receptor activity. Predicted to be involved in several processes, including axon guidance; positive regulation of axonogenesis; and regulation of GTPase activity. Predicted to act upstream of or within several processes, including nervous system development; regulation of axon extension involved in axon guidance; and regulation of negative chemotaxis. Predicted to be located in plasma membrane. Predicted to be part of semaphorin receptor complex. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA4	NM_020911.2	c.5492C>G	p.Ala1831Gly	missense_variant	31/32	ENST00000321063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA4	ENST00000321063.9	c.5492C>G	p.Ala1831Gly	missense_variant	31/32	5	NM_020911.2	P1
PLXNA4	ENST00000359827.7	c.5492C>G	p.Ala1831Gly	missense_variant	31/32	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

PLXNA4-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 14, 2023

The PLXNA4 c.5492C>G variant is predicted to result in the amino acid substitution p.Ala1831Gly. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;.
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.0	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.99	D;D
Vest4		0.81
MutPred		0.49		Gain of disorder (P = 0.1171);Gain of disorder (P = 0.1171);
MVP		0.50
MPC		1.6
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.71
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-131817905;