rs11920311

Variant names:

• chr3-129556363-C-T
• rs11920311
• NM_015103.3:c.5727G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_015103.3(PLXND1):​c.5727G>A​(p.Gln1909Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,730 control chromosomes in the GnomAD database, including 20,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.19 (3157 hom., cov: 33)
  • Exomes 𝑓: 0.15 (17184 hom.)
• Consequence: PLXND1 NM_015103.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.650
• Publications: 15 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=-0.38).
• BP6: Variant 3-129556363-C-T is Benign according to our data. Variant chr3-129556363-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059889.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 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.5727G>A	p.Gln1909Gln	synonymous	Exon 36 of 36	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.5727G>A	p.Gln1909Gln	synonymous	Exon 36 of 36	ENSP00000317128.4	Q9Y4D7-1
	PLXND1	ENST00000501038.6	TSL:1	n.484G>A		non_coding_transcript_exon	Exon 2 of 2
	PLXND1	ENST00000504524.5	TSL:1	n.552G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28432 AN: 152118 Hom.: 3140 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0829

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.178

GnomAD2 exomes AF: 0.168 AC: 42319 AN: 251442 AF XY: 0.167

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.223

Gnomad FIN exome AF: 0.0778

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.146 AC: 212675 AN: 1461494 Hom.: 17184 Cov.: 32 AF XY: 0.148 AC XY: 107617 AN XY: 727066

African (AFR) AF: 0.297 AC: 9928 AN: 33466

American (AMR) AF: 0.219 AC: 9803 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 4266 AN: 26130

East Asian (EAS) AF: 0.256 AC: 10146 AN: 39696

South Asian (SAS) AF: 0.233 AC: 20091 AN: 86244

European-Finnish (FIN) AF: 0.0794 AC: 4241 AN: 53418

Middle Eastern (MID) AF: 0.154 AC: 888 AN: 5768

European-Non Finnish (NFE) AF: 0.129 AC: 143937 AN: 1111678

Other (OTH) AF: 0.155 AC: 9375 AN: 60382

GnomAD4 genome AF: 0.187 AC: 28485 AN: 152236 Hom.: 3157 Cov.: 33 AF XY: 0.190 AC XY: 14118 AN XY: 74440

African (AFR) AF: 0.289 AC: 12019 AN: 41520

American (AMR) AF: 0.234 AC: 3581 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1194 AN: 5172

South Asian (SAS) AF: 0.227 AC: 1097 AN: 4832

European-Finnish (FIN) AF: 0.0829 AC: 880 AN: 10616

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8593 AN: 68012

Other (OTH) AF: 0.176 AC: 373 AN: 2116

Alfa AF: 0.150 Hom.: 7785

Bravo AF: 0.200

Asia WGS AF: 0.223 AC: 778 AN: 3478

EpiCase AF: 0.136

EpiControl AF: 0.140

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PLXND1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	5.6
DANN	Benign	0.88
PhyloP100		0.65
Mutation Taster		=98/2	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: rs11920311; hg19: chr3-129275206; COSMIC: COSV60712281; COSMIC: COSV60712281;