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GeneBe

3-129557179-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_015103.3(PLXND1):c.5490G>A(p.Glu1830=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,614,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

PLXND1
NM_015103.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21
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 Likely_benign. Variant got -3 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.35).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-129557179-C-T is Benign according to our data. Variant chr3-129557179-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 736030.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=1.21 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLXND1NM_015103.3 linkuse as main transcriptc.5490G>A p.Glu1830= synonymous_variant 34/36 ENST00000324093.9
PLXND1XM_011512588.3 linkuse as main transcriptc.5490G>A p.Glu1830= synonymous_variant 34/36
PLXND1XM_011512589.2 linkuse as main transcriptc.5100G>A p.Glu1700= synonymous_variant 31/33
PLXND1XM_011512592.1 linkuse as main transcriptc.2658G>A p.Glu886= synonymous_variant 22/24

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLXND1ENST00000324093.9 linkuse as main transcriptc.5490G>A p.Glu1830= synonymous_variant 34/361 NM_015103.3 P1Q9Y4D7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000282
AC:
43
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000470
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000259
AC:
65
AN:
251426
Hom.:
0
AF XY:
0.000272
AC XY:
37
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.000422
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000538
AC:
786
AN:
1461852
Hom.:
0
Cov.:
32
AF XY:
0.000509
AC XY:
370
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000635
Gnomad4 OTH exome
AF:
0.000828
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000282
AC:
43
AN:
152334
Hom.:
0
Cov.:
32
AF XY:
0.000282
AC XY:
21
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000470
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000442
Hom.:
0
Bravo
AF:
0.000366
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000654
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.35
Cadd
Benign
7.5
Dann
Benign
0.83

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: rs143899582; hg19: chr3-129276022; API