6-3727577-C-T

Position:

• chr6-3727577-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_183373.4(PXDC1):​c.552G>A​(p.Gln184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PXDC1 NM_183373.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.975

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.975 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDC1	NM_183373.4	c.552G>A	p.Gln184=	synonymous_variant	4/5	ENST00000380283.5	NP_899229.2
PXDC1	XM_011514393.4	c.369G>A	p.Gln123=	synonymous_variant	5/6		XP_011512695.1
PXDC1	XM_047418376.1	c.369G>A	p.Gln123=	synonymous_variant	4/5		XP_047274332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDC1	ENST00000380283.5	c.552G>A	p.Gln184=	synonymous_variant	4/5	1	NM_183373.4	ENSP00000369636	P1
PXDC1	ENST00000380277.6	c.396G>A	p.Gln132=	synonymous_variant	4/5	3		ENSP00000369630
PXDC1	ENST00000477592.2	n.548G>A		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459548 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726342

Gnomad4 AFR exome AF: 0.00

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.0
DANN	Benign	0.69

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: rs226959; hg19: chr6-3727811;