chr3-129556666-T-G

Variant names:

• chr3-129556666-T-G
• rs200118477
• NM_015103.3:c.5612A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015103.3(PLXND1):​c.5612A>C​(p.Asn1871Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLXND1 NM_015103.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

Genes affected

PLXND1 (HGNC:9107): (plexin D1) Enables protein domain specific binding activity. Predicted to be involved in several processes, including endothelial cell migration; nervous system development; and regulation of angiogenesis. Predicted to act upstream of or within several processes, including circulatory system development; dichotomous subdivision of terminal units involved in salivary gland branching; and positive regulation of protein binding activity. Located in lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34801072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXND1	NM_015103.3	c.5612A>C	p.Asn1871Thr	missense_variant	Exon 35 of 36	ENST00000324093.9	NP_055918.3
PLXND1	XM_011512588.3	c.5612A>C	p.Asn1871Thr	missense_variant	Exon 35 of 36		XP_011510890.1
PLXND1	XM_011512589.2	c.5222A>C	p.Asn1741Thr	missense_variant	Exon 32 of 33		XP_011510891.1
PLXND1	XM_011512592.1	c.2780A>C	p.Asn927Thr	missense_variant	Exon 23 of 24		XP_011510894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXND1	ENST00000324093.9	c.5612A>C	p.Asn1871Thr	missense_variant	Exon 35 of 36	1	NM_015103.3	ENSP00000317128.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460816 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726688

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.095	T;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N;D
REVEL	Benign	0.11
Sift	Benign	0.17	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.10	B;.
Vest4		0.47
MutPred		0.47		Loss of MoRF binding (P = 0.1426);.;
MVP		0.54
MPC		0.90
ClinPred		0.69	D
GERP RS		5.1
Varity_R		0.18
gMVP		0.30

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: rs200118477; hg19: chr3-129275509;