Menu
GeneBe

3-129556363-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_015103.3(PLXND1):c.5727G>A(p.Gln1909=) 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 (★).

Frequency

Genomes: 𝑓 0.19 ( 3157 hom., cov: 33)
Exomes 𝑓: 0.15 ( 17184 hom. )

Consequence

PLXND1
NM_015103.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.650
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-129556363-C-T is Benign according to our data. Variant chr3-129556363-C-T is described in ClinVar as [Benign]. Clinvar id is 3059889.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.65 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLXND1NM_015103.3 linkuse as main transcriptc.5727G>A p.Gln1909= synonymous_variant 36/36 ENST00000324093.9
PLXND1XM_011512589.2 linkuse as main transcriptc.5337G>A p.Gln1779= synonymous_variant 33/33
PLXND1XM_011512592.1 linkuse as main transcriptc.2895G>A p.Gln965= synonymous_variant 24/24
PLXND1XM_011512588.3 linkuse as main transcriptc.*84G>A 3_prime_UTR_variant 36/36

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLXND1ENST00000324093.9 linkuse as main transcriptc.5727G>A p.Gln1909= synonymous_variant 36/361 NM_015103.3 P1Q9Y4D7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.187
AC:
28432
AN:
152118
Hom.:
3140
Cov.:
33
show subpopulations
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
GnomAD3 exomes
AF:
0.168
AC:
42319
AN:
251442
Hom.:
4131
AF XY:
0.167
AC XY:
22681
AN XY:
135892
show subpopulations
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 SAS exome
AF:
0.235
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
show subpopulations
Gnomad4 AFR exome
AF:
0.297
Gnomad4 AMR exome
AF:
0.219
Gnomad4 ASJ exome
AF:
0.163
Gnomad4 EAS exome
AF:
0.256
Gnomad4 SAS exome
AF:
0.233
Gnomad4 FIN exome
AF:
0.0794
Gnomad4 NFE exome
AF:
0.129
Gnomad4 OTH exome
AF:
0.155
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.187
AC:
28485
AN:
152236
Hom.:
3157
Cov.:
33
AF XY:
0.190
AC XY:
14118
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.289
Gnomad4 AMR
AF:
0.234
Gnomad4 ASJ
AF:
0.165
Gnomad4 EAS
AF:
0.231
Gnomad4 SAS
AF:
0.227
Gnomad4 FIN
AF:
0.0829
Gnomad4 NFE
AF:
0.126
Gnomad4 OTH
AF:
0.176
Alfa
AF:
0.146
Hom.:
3382
Bravo
AF:
0.200
Asia WGS
AF:
0.223
AC:
778
AN:
3478
EpiCase
AF:
0.136
EpiControl
AF:
0.140

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PLXND1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 06, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
5.6
Dann
Benign
0.88

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11920311; hg19: chr3-129275206; COSMIC: COSV60712281; COSMIC: COSV60712281; API