chr17-39087622-A-G

Position:

• chr17-39087622-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020405.5(PLXDC1):​c.892T>C​(p.Phe298Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLXDC1 NM_020405.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.69

Genes affected

PLXDC1 (HGNC:20945): (plexin domain containing 1) Predicted to be involved in angiogenesis and spinal cord development. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

RDM1P5 (HGNC:53921): (RDM1 pseudogene 5)

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37399718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXDC1	NM_020405.5	c.892T>C	p.Phe298Leu	missense_variant	8/14	ENST00000315392.9
RDM1P5	NR_174975.1	n.1305+516A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXDC1	ENST00000315392.9	c.892T>C	p.Phe298Leu	missense_variant	8/14	1	NM_020405.5	P1
RDM1P5	ENST00000578423.1	n.326-19795A>G		intron_variant, non_coding_transcript_variant		5
	ENST00000667388.1	n.131+516A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.892T>C (p.F298L) alteration is located in exon 8 (coding exon 8) of the PLXDC1 gene. This alteration results from a T to C substitution at nucleotide position 892, causing the phenylalanine (F) at amino acid position 298 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0099	T;T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.90	L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Uncertain	0.36
Sift	Benign	0.35	T;T;.
Sift4G	Benign	0.85	T;T;.
Polyphen		0.99	D;P;.
Vest4		0.79
MutPred		0.33		Gain of disorder (P = 0.1);.;.;
MVP		0.66
MPC		0.94
ClinPred		0.90	D
GERP RS		6.0
Varity_R		0.10
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-37243875;