16-21988775-A-G

Position:

• chr16-21988775-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001363519.1(PDZD9):​c.228T>C​(p.Ser76=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000758 in 1,609,220 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00080 (2 hom.)
• Consequence: PDZD9 NM_001363519.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.299

Genes affected

PDZD9 (HGNC:28740): (PDZ domain containing 9)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 16-21988775-A-G is Benign according to our data. Variant chr16-21988775-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2646308.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.299 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD9	NM_001363519.1	c.228T>C	p.Ser76=	synonymous_variant	3/4	ENST00000424898.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD9	ENST00000424898.3	c.228T>C	p.Ser76=	synonymous_variant	3/4	5	NM_001363519.1	P1
PDZD9	ENST00000523914.5	c.*5T>C		3_prime_UTR_variant, NMD_transcript_variant	4/5	1
PDZD9	ENST00000537222.6	c.48T>C	p.Ser16=	synonymous_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152204 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000557 AC: 137 AN: 246178 Hom.: 0 AF XY: 0.000638 AC XY: 85 AN XY: 133238

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000362

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.0000490

Gnomad NFE exome AF: 0.000755

Gnomad OTH exome AF: 0.000664

GnomAD4 exome AF: 0.000802 AC: 1169 AN: 1456898 Hom.: 2 Cov.: 31 AF XY: 0.000884 AC XY: 641 AN XY: 724822

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.000345

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00151

Gnomad4 FIN exome AF: 0.0000385

Gnomad4 NFE exome AF: 0.000896

Gnomad4 OTH exome AF: 0.000432

GnomAD4 genome AF: 0.000335 AC: 51 AN: 152322 Hom.: 0 Cov.: 31 AF XY: 0.000282 AC XY: 21 AN XY: 74484

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000397 Hom.: 0

Bravo AF: 0.000404

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000819

EpiControl AF: 0.000653

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

PDZD9: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.4
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs149154019; hg19: chr16-22000096;