rs144469613

Variant names:

• chr10-101019138-G-A
• rs144469613
• NM_001195263.2:c.1008C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-101019138-G-A
• chr10-101019138-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001195263.2(PDZD7):​c.1008C>T​(p.Pro336Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00823 in 1,545,728 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P336P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0070 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (57 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.24
• Publications: 3 publications found

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]

PDZD7 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: Unknown Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive 57

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Usher syndrome type 2C

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 10-101019138-G-A is Benign according to our data. Variant chr10-101019138-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00696 (1061/152388) while in subpopulation NFE AF = 0.00961 (654/68036). AF 95% confidence interval is 0.009. There are 4 homozygotes in GnomAd4. There are 534 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195263.2. 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
	PDZD7	NM_001195263.2	MANE Select	c.1008C>T	p.Pro336Pro	synonymous	Exon 8 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.1008C>T	p.Pro336Pro	synonymous	Exon 8 of 17	NP_001424358.1
	PDZD7	NM_001351044.2		c.1008C>T	p.Pro336Pro	synonymous	Exon 8 of 10	NP_001337973.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.1008C>T	p.Pro336Pro	synonymous	Exon 8 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.1008C>T	p.Pro336Pro	synonymous	Exon 8 of 17	ENSP00000582249.1
	PDZD7	ENST00000645349.1		c.1008C>T	p.Pro336Pro	synonymous	Exon 8 of 10	ENSP00000495283.1	A0A2R8YFN1

Frequencies

GnomAD3 genomes AF: 0.00697 AC: 1061 AN: 152270 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00837

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00961

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00629 AC: 926 AN: 147152 AF XY: 0.00629

Gnomad AFR exome AF: 0.00128

Gnomad AMR exome AF: 0.00495

Gnomad ASJ exome AF: 0.00651

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00867

Gnomad NFE exome AF: 0.00992

Gnomad OTH exome AF: 0.00769

GnomAD4 exome AF: 0.00837 AC: 11658 AN: 1393340 Hom.: 57 Cov.: 33 AF XY: 0.00821 AC XY: 5654 AN XY: 688628

African (AFR) AF: 0.00130 AC: 42 AN: 32282

American (AMR) AF: 0.00497 AC: 183 AN: 36804

Ashkenazi Jewish (ASJ) AF: 0.00727 AC: 183 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 36712

South Asian (SAS) AF: 0.00267 AC: 213 AN: 79888

European-Finnish (FIN) AF: 0.00752 AC: 263 AN: 34954

Middle Eastern (MID) AF: 0.00504 AC: 27 AN: 5358

European-Non Finnish (NFE) AF: 0.00956 AC: 10358 AN: 1083954

Other (OTH) AF: 0.00668 AC: 389 AN: 58202

GnomAD4 genome AF: 0.00696 AC: 1061 AN: 152388 Hom.: 4 Cov.: 32 AF XY: 0.00717 AC XY: 534 AN XY: 74520

African (AFR) AF: 0.00195 AC: 81 AN: 41602

American (AMR) AF: 0.00836 AC: 128 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4834

European-Finnish (FIN) AF: 0.0123 AC: 131 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00961 AC: 654 AN: 68036

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00470 Hom.: 0

Bravo AF: 0.00628

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		1.2
Mutation Taster		=99/1	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: rs144469613; hg19: chr10-102778895;