NM_001303512.2:c.1618C>T

Variant names:

• chrX-153804063-G-A
• rs892206256
• NM_001303512.2:c.1618C>T

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.1618C>T​(p.Pro540Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,044,160 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000029 (0 hom. 1 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.00
• 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=0.049129397).

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.1618C>T	p.Pro540Ser	missense	Exon 8 of 8	NP_001290441.1	Q17RL8
	PDZD4	NM_032512.5		c.1600C>T	p.Pro534Ser	missense	Exon 8 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.1375C>T	p.Pro459Ser	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.1618C>T	p.Pro540Ser	missense	Exon 8 of 8	ENSP00000377355.3	Q17RL8
	PDZD4	ENST00000164640.8	TSL:1	c.1600C>T	p.Pro534Ser	missense	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
	PDZD4	ENST00000544474.5	TSL:1	c.1273C>T	p.Pro425Ser	missense	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000287 AC: 3 AN: 1044160 Hom.: 0 Cov.: 33 AF XY: 0.00000294 AC XY: 1 AN XY: 339990

African (AFR) AF: 0.00 AC: 0 AN: 24817

American (AMR) AF: 0.0000363 AC: 1 AN: 27550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18441

East Asian (EAS) AF: 0.00 AC: 0 AN: 27077

South Asian (SAS) AF: 0.00 AC: 0 AN: 49363

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3790

European-Non Finnish (NFE) AF: 0.00000244 AC: 2 AN: 818314

Other (OTH) AF: 0.00 AC: 0 AN: 44136

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.20
DANN	Benign	0.43
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.42	N
PhyloP100		-1.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.014
Sift	Benign	0.33	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.021
MutPred		0.19		Gain of phosphorylation at P534 (P = 0.003)
MVP		0.093
MPC		0.90
ClinPred		0.13	T
GERP RS		0.49
Varity_R		0.048
gMVP		0.37
Mutation Taster		=98/2	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: rs892206256; hg19: chrX-153069518;