chrX-153807337-G-A

Variant names:

• chrX-153807337-G-A
• rs368296370
• NM_001303512.2:c.347C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001303512.2(PDZD4):​c.347C>T​(p.Ala116Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,208,390 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. 12/21 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. A116E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.0000046 (0 hom. 1 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07194489).

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.347C>T	p.Ala116Val	missense	Exon 3 of 8	NP_001290441.1	Q17RL8
	PDZD4	NM_032512.5		c.329C>T	p.Ala110Val	missense	Exon 3 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.104C>T	p.Ala35Val	missense	Exon 3 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.347C>T	p.Ala116Val	missense	Exon 3 of 8	ENSP00000377355.3	Q17RL8
	PDZD4	ENST00000164640.8	TSL:1	c.329C>T	p.Ala110Val	missense	Exon 3 of 8	ENSP00000164640.4	Q76G19-1
	PDZD4	ENST00000544474.5	TSL:1	c.61-497C>T		intron	N/A	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes AF: 0.0000177 AC: 2 AN: 112826 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000114 AC: 2 AN: 176163 AF XY: 0.0000160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000658

Gnomad NFE exome AF: 0.0000128

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000456 AC: 5 AN: 1095564 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 1 AN XY: 361540

African (AFR) AF: 0.00 AC: 0 AN: 26383

American (AMR) AF: 0.00 AC: 0 AN: 35057

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19313

East Asian (EAS) AF: 0.00 AC: 0 AN: 30151

South Asian (SAS) AF: 0.0000373 AC: 2 AN: 53634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39657

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4124

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 841239

Other (OTH) AF: 0.00 AC: 0 AN: 46006

GnomAD4 genome AF: 0.0000177 AC: 2 AN: 112826 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 35006

African (AFR) AF: 0.00 AC: 0 AN: 31082

American (AMR) AF: 0.00 AC: 0 AN: 10794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3565

South Asian (SAS) AF: 0.00 AC: 0 AN: 2816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6275

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53198

Other (OTH) AF: 0.00 AC: 0 AN: 1524

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	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.039
Sift	Benign	0.24	T
Sift4G	Benign	0.30	T
Polyphen		0.12	B
Vest4		0.097
MutPred		0.32		Loss of relative solvent accessibility (P = 0.0981)
MVP		0.36
MPC		0.10
ClinPred		0.43	T
GERP RS		5.6
Varity_R		0.14
gMVP		0.61
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs368296370; hg19: chrX-153072792; COSMIC: COSV51248679;