X-153803412-C-A

Variant names:

• chrX-153803412-C-A
• rs968113390
• NM_001303512.2:c.2269G>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.2269G>T​(p.Ala757Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000097 in 1,030,917 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. 16/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A757T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.7e-7 (0 hom. 0 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• 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=0.041013837).

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.2269G>T	p.Ala757Ser	missense	Exon 8 of 8	NP_001290441.1	Q17RL8
	PDZD4	NM_032512.5		c.2251G>T	p.Ala751Ser	missense	Exon 8 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.2026G>T	p.Ala676Ser	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.2269G>T	p.Ala757Ser	missense	Exon 8 of 8	ENSP00000377355.3	Q17RL8
	PDZD4	ENST00000164640.8	TSL:1	c.2251G>T	p.Ala751Ser	missense	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
	PDZD4	ENST00000544474.5	TSL:1	c.1924G>T	p.Ala642Ser	missense	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.70e-7 AC: 1 AN: 1030917 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 332567

African (AFR) AF: 0.00 AC: 0 AN: 23752

American (AMR) AF: 0.00 AC: 0 AN: 23226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14933

East Asian (EAS) AF: 0.00 AC: 0 AN: 29583

South Asian (SAS) AF: 0.00 AC: 0 AN: 44553

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36787

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3800

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 811222

Other (OTH) AF: 0.00 AC: 0 AN: 43061

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.0
DANN	Benign	0.74
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		1.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.040
Sift	Benign	0.48	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.37
MPC		0.82
ClinPred		0.071	T
GERP RS		3.5
Varity_R		0.035
gMVP		0.62
Mutation Taster		=92/8	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: rs968113390; hg19: chrX-153068867;