10-101008423-C-T

Position:

• chr10-101008423-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001195263.2(PDZD7):​c.*44G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000726 in 1,462,422 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 0.00097 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00070 (1 hom.)
• Consequence: PDZD7 NM_001195263.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.84

Genes affected

PDZD7 (HGNC:26257): (PDZ domain containing 7) This gene encodes a ciliary protein homologous to proteins which are mutated in Usher syndrome patients, and mutations and translocations involving this gene have been associated with two types of Usher syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-101008423-C-T is Benign according to our data. Variant chr10-101008423-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1254533.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000972 (146/150136) while in subpopulation EAS AF= 0.00869 (44/5066). AF 95% confidence interval is 0.00665. There are 1 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD7	NM_001195263.2	c.*44G>A		3_prime_UTR_variant	17/17	ENST00000619208.6
PDZD7	XM_011540177.4	c.*44G>A		3_prime_UTR_variant	18/18
PDZD7	XM_011540178.4	c.*44G>A		3_prime_UTR_variant	17/17
PDZD7	XM_047425767.1	c.*44G>A		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD7	ENST00000619208.6	c.*44G>A		3_prime_UTR_variant	17/17	5	NM_001195263.2	P1
PDZD7	ENST00000474125.7	c.*3093G>A		3_prime_UTR_variant, NMD_transcript_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.000973 AC: 146 AN: 150012 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000519

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00285

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00866

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000443

Gnomad OTH AF: 0.00387

GnomAD3 exomes AF: 0.00180 AC: 159 AN: 88518 Hom.: 0 AF XY: 0.00158 AC XY: 71 AN XY: 45040

Gnomad AFR exome AF: 0.000319

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00716

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000735

Gnomad OTH exome AF: 0.00280

GnomAD4 exome AF: 0.000697 AC: 915 AN: 1312286 Hom.: 1 Cov.: 31 AF XY: 0.000725 AC XY: 464 AN XY: 639852

Gnomad4 AFR exome AF: 0.000235

Gnomad4 AMR exome AF: 0.00259

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00404

Gnomad4 SAS exome AF: 0.0000440

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000567

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.000972 AC: 146 AN: 150136 Hom.: 1 Cov.: 31 AF XY: 0.000969 AC XY: 71 AN XY: 73256

Gnomad4 AFR AF: 0.000518

Gnomad4 AMR AF: 0.00284

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00869

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000443

Gnomad4 OTH AF: 0.00383

Alfa AF: 0.000429 Hom.: 0

Bravo AF: 0.00121

Asia WGS AF: 0.00462 AC: 16 AN: 3478

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

GeneDx

Feb 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.40
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs150768091; hg19: chr10-102768180;