NM_032812.9:c.8G>C

Variant names:

• chr10-19817087-G-C
• rs772703697
• NM_032812.9:c.8G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032812.9(PLXDC2):​c.8G>C​(p.Arg3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PLXDC2 NM_032812.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• Publications: 0 publications found

Genes affected

PLXDC2 (HGNC:21013): (plexin domain containing 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285852 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24340865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9	c.8G>C	p.Arg3Thr	missense_variant	Exon 1 of 14	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.8G>C	p.Arg3Thr	missense_variant	Exon 1 of 13		NP_001269665.1
PLXDC2	XM_011519750.3	c.8G>C	p.Arg3Thr	missense_variant	Exon 1 of 14		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXDC2	ENST00000377252.5	c.8G>C	p.Arg3Thr	missense_variant	Exon 1 of 14	1	NM_032812.9	ENSP00000366460.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400050 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 691076

African (AFR) AF: 0.00 AC: 0 AN: 31638

American (AMR) AF: 0.00 AC: 0 AN: 36430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25316

East Asian (EAS) AF: 0.00 AC: 0 AN: 35850

South Asian (SAS) AF: 0.00 AC: 0 AN: 79706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5474

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079840

Other (OTH) AF: 0.00 AC: 0 AN: 58050

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L;L
PhyloP100		3.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.91	N;N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.98	D;D
Vest4		0.42
MutPred		0.24		Gain of glycosylation at R3 (P = 0.0136);Gain of glycosylation at R3 (P = 0.0136);
MVP		0.21
MPC		0.18
ClinPred		0.82	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.44
gMVP		0.37
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs772703697; hg19: chr10-20106016;