X-153803869-G-T

Variant names:

• chrX-153803869-G-T
• rs782807192
• NM_001303512.2:c.1812C>A

Variant summary

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

The NM_001303512.2(PDZD4):​c.1812C>A​(p.His604Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000932 in 1,072,530 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 0 publications found

Genes affected

PDZD4 (HGNC:21167): (PDZ domain containing 4) Predicted to be located in cell cortex. [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=0.023365825).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303512.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD4	NM_001303512.2	MANE Select	c.1812C>A	p.His604Gln	missense	Exon 8 of 8	NP_001290441.1	Q17RL8
	PDZD4	NM_032512.5		c.1794C>A	p.His598Gln	missense	Exon 8 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.1569C>A	p.His523Gln	missense	Exon 8 of 8	NP_001290444.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD4	ENST00000393758.7	TSL:1 MANE Select	c.1812C>A	p.His604Gln	missense	Exon 8 of 8	ENSP00000377355.3	Q17RL8
	PDZD4	ENST00000164640.8	TSL:1	c.1794C>A	p.His598Gln	missense	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
	PDZD4	ENST00000544474.5	TSL:1	c.1467C>A	p.His489Gln	missense	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.32e-7 AC: 1 AN: 1072530 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 347140

African (AFR) AF: 0.00 AC: 0 AN: 25847

American (AMR) AF: 0.00 AC: 0 AN: 33173

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18464

East Asian (EAS) AF: 0.00 AC: 0 AN: 29635

South Asian (SAS) AF: 0.00 AC: 0 AN: 51362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3904

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 832183

Other (OTH) AF: 0.00 AC: 0 AN: 45064

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.27
DEOGEN2	Benign	0.084	T
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.82	N
PhyloP100		-2.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.026
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.060
MutPred		0.15		Gain of relative solvent accessibility (P = 0.09)
MVP		0.20
MPC		0.90
ClinPred		0.037	T
GERP RS		-5.0
Varity_R		0.044
gMVP		0.51
Mutation Taster		=100/0	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: rs782807192; hg19: chrX-153069324;