3-129577177-C-T

Variant names:

• chr3-129577177-C-T
• rs2625961
• NM_015103.3:c.2346+1152G>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.2346+1152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,100 control chromosomes in the GnomAD database, including 6,426 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 0.28 (6426 hom., cov: 32)
• Consequence: PLXND1 NM_015103.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 7 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Mobius syndrome

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015103.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXND1	NM_015103.3	MANE Select	c.2346+1152G>A		intron	N/A	NP_055918.3	Q9Y4D7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXND1	ENST00000324093.9	TSL:1 MANE Select	c.2346+1152G>A		intron	N/A	ENSP00000317128.4	Q9Y4D7-1
	PLXND1	ENST00000891948.1		c.2346+1152G>A		intron	N/A	ENSP00000562007.1
	PLXND1	ENST00000505505.1	TSL:2	n.220+1152G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42587 AN: 151982 Hom.: 6405 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.280 AC: 42648 AN: 152100 Hom.: 6426 Cov.: 32 AF XY: 0.282 AC XY: 20942 AN XY: 74368

African (AFR) AF: 0.365 AC: 15135 AN: 41482

American (AMR) AF: 0.246 AC: 3763 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1312 AN: 3466

East Asian (EAS) AF: 0.495 AC: 2544 AN: 5144

South Asian (SAS) AF: 0.266 AC: 1283 AN: 4832

European-Finnish (FIN) AF: 0.226 AC: 2394 AN: 10600

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15344 AN: 67966

Other (OTH) AF: 0.293 AC: 618 AN: 2108

Alfa AF: 0.241 Hom.: 602

Bravo AF: 0.288

Asia WGS AF: 0.363 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		-0.32
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: rs2625961; hg19: chr3-129296020;