6-3727566-T-A

Position:

• chr6-3727566-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_183373.4(PXDC1):​c.563A>T​(p.Asp188Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PXDC1 NM_183373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.55

Genes affected

PXDC1 (HGNC:21361): (PX domain containing 1) Predicted to enable phosphatidylinositol binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PXDC1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.752

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDC1	NM_183373.4	c.563A>T	p.Asp188Val	missense_variant	4/5	ENST00000380283.5	NP_899229.2
PXDC1	XM_011514393.4	c.380A>T	p.Asp127Val	missense_variant	5/6		XP_011512695.1
PXDC1	XM_047418376.1	c.380A>T	p.Asp127Val	missense_variant	4/5		XP_047274332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDC1	ENST00000380283.5	c.563A>T	p.Asp188Val	missense_variant	4/5	1	NM_183373.4	ENSP00000369636.5
PXDC1	ENST00000380277.6	c.404A>T	p.Asp135Val	missense_variant	4/5	3		ENSP00000369630.2
PXDC1	ENST00000477592.2	n.559A>T		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

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

Dec 03, 2021

The c.563A>T (p.D188V) alteration is located in exon 4 (coding exon 4) of the PXDC1 gene. This alteration results from a A to T substitution at nucleotide position 563, causing the aspartic acid (D) at amino acid position 188 to be replaced by a valine (V). 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	Benign	0.18
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.057	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.016	D
Polyphen		0.95	P
Vest4		0.88
MutPred		0.40		Gain of sheet (P = 0.0125);
MVP		0.39
MPC		0.75
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.52
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-3727800;