rs226959

Variant names:

• chr6-3727577-C-A
• rs226959
• NM_183373.4:c.552G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-3727577-C-A
• chr6-3727577-C-G
• chr6-3727577-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_183373.4(PXDC1):​c.552G>T​(p.Gln184His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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: 6.9e-7 (0 hom.)
• Consequence: PXDC1 NM_183373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.975
• Publications: 39 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040963233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDC1	NM_183373.4	c.552G>T	p.Gln184His	missense_variant	Exon 4 of 5	ENST00000380283.5	NP_899229.2
PXDC1	XM_011514393.4	c.369G>T	p.Gln123His	missense_variant	Exon 5 of 6		XP_011512695.1
PXDC1	XM_047418376.1	c.369G>T	p.Gln123His	missense_variant	Exon 4 of 5		XP_047274332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXDC1	ENST00000380283.5	c.552G>T	p.Gln184His	missense_variant	Exon 4 of 5	1	NM_183373.4	ENSP00000369636.5
PXDC1	ENST00000380277.6	c.393G>T	p.Gln131His	missense_variant	Exon 4 of 5	3		ENSP00000369630.2
PXDC1	ENST00000477592.2	n.548G>T		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459548 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726342

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109884

Other (OTH) AF: 0.0000166 AC: 1 AN: 60324

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.97
PrimateAI	Benign	0.32	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.10
Sift	Benign	0.29	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.034
MutPred		0.079		Gain of disorder (P = 0.1614);
MVP		0.068
MPC		0.38
ClinPred		0.80	D
GERP RS		4.5
Varity_R		0.045
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs226959; hg19: chr6-3727811;