Genetic Variant NM_015103.3:c.5446-10_5446-7dupCTCT (chr3-129557229-C-CAGAG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_015103.3(PLXND1):c.5446-10_5446-7dupCTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,613,906 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 1 hom. )

Consequence

PLXND1
NM_015103.3 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.505

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]

PLXND1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 3-129557229-C-CAGAG is Benign according to our data. Variant chr3-129557229-C-CAGAG is described in ClinVar as [Likely_benign]. Clinvar id is 722559.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PLXND1	NM_015103.3 link	c.5446-10_5446-7dupCTCT	splice_region_variant, intron_variant	Intron 33 of 35	ENST00000324093.9	NP_055918.3	Q9Y4D7-1
PLXND1	XM_011512588.3 link	c.5446-10_5446-7dupCTCT	splice_region_variant, intron_variant	Intron 33 of 35		XP_011510890.1
PLXND1	XM_011512589.2 link	c.5056-10_5056-7dupCTCT	splice_region_variant, intron_variant	Intron 30 of 32		XP_011510891.1
PLXND1	XM_011512592.1 link	c.2614-10_2614-7dupCTCT	splice_region_variant, intron_variant	Intron 21 of 23		XP_011510894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXND1	ENST00000324093.9 link	c.5446-7_5446-6insCTCT		splice_region_variant, intron_variant	Intron 33 of 35	1	NM_015103.3	ENSP00000317128.4		Q9Y4D7-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000955

AC:

AN:

251260

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000314

AC:

459

AN:

1461726

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

220

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000378

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.000158

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000166

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PLXND1-related disorder

Benign:1

Jul 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over