chr3-129580151-G-T

Variant names:

• chr3-129580151-G-T
• rs10934885
• NM_015103.3:c.2242-1718C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015103.3(PLXND1):​c.2242-1718C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,110 control chromosomes in the GnomAD database, including 47,227 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (47227 hom., cov: 32)
• Consequence: PLXND1 NM_015103.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 4 publications found

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]

PLXND1 Gene-Disease associations (from GenCC):

• congenital heart defects, multiple types, 9

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Mobius syndrome

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P
• persistent truncus arteriosus

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXND1	NM_015103.3	c.2242-1718C>A		intron_variant	Intron 8 of 35	ENST00000324093.9	NP_055918.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXND1	ENST00000324093.9	c.2242-1718C>A		intron_variant	Intron 8 of 35	1	NM_015103.3	ENSP00000317128.4

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119530 AN: 151992 Hom.: 47189 Cov.: 32

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.772

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.786 AC: 119618 AN: 152110 Hom.: 47227 Cov.: 32 AF XY: 0.786 AC XY: 58454 AN XY: 74326

African (AFR) AF: 0.781 AC: 32434 AN: 41514

American (AMR) AF: 0.794 AC: 12136 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2578 AN: 3468

East Asian (EAS) AF: 0.617 AC: 3164 AN: 5128

South Asian (SAS) AF: 0.797 AC: 3844 AN: 4824

European-Finnish (FIN) AF: 0.812 AC: 8593 AN: 10586

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54268 AN: 67992

Other (OTH) AF: 0.773 AC: 1632 AN: 2112

Alfa AF: 0.789 Hom.: 196044

Bravo AF: 0.783

Asia WGS AF: 0.742 AC: 2576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.095
DANN	Benign	0.38
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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: rs10934885; hg19: chr3-129298994;