6-3751435-C-T

Position:

• chr6-3751435-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_183373.4(PXDC1):​c.97G>A​(p.Gly33Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,438,774 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PXDC1 NM_183373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.66

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDC1	NM_183373.4	c.97G>A	p.Gly33Ser	missense_variant	1/5	ENST00000380283.5	NP_899229.2
PXDC1	XR_007059222.1	n.279G>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDC1	ENST00000380283.5	c.97G>A	p.Gly33Ser	missense_variant	1/5	1	NM_183373.4	ENSP00000369636.5
PXDC1	ENST00000477592.2	n.98G>A		non_coding_transcript_exon_variant	1/5	5
PXDC1	ENST00000485986.1	n.95G>A		non_coding_transcript_exon_variant	1/3	2
ENSG00000270504	ENST00000603791.1	n.325C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438774 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 713670

Gnomad4 AFR exome AF: 0.0000609

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000698 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.000233 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000840 AC: 1

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

Feb 28, 2024

The c.97G>A (p.G33S) alteration is located in exon 1 (coding exon 1) of the PXDC1 gene. This alteration results from a G to A substitution at nucleotide position 97, causing the glycine (G) at amino acid position 33 to be replaced by a serine (S). 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	0.33
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.84	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.64
MVP		0.20
MPC		1.2
ClinPred		1.0	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.89
gMVP		0.61

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

Other links and lift over

dbSNP: rs199973288; hg19: chr6-3751669;