rs1273046835

Variant names:

• chr10-101008578-G-A
• rs1273046835
• NM_001195263.2:c.2991C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-101008578-G-A
• chr10-101008578-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001195263.2(PDZD7):​c.2991C>T​(p.Pro997Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000361 in 1,383,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P997P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 0 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: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive 57

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=1.34 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2	c.2991C>T	p.Pro997Pro	synonymous_variant	Exon 17 of 17	ENST00000619208.6	NP_001182192.1
PDZD7	NM_001437429.1	c.2988C>T	p.Pro996Pro	synonymous_variant	Exon 17 of 17		NP_001424358.1
PDZD7	XM_011540177.4	c.2991C>T	p.Pro997Pro	synonymous_variant	Exon 18 of 18		XP_011538479.1
PDZD7	XM_047425767.1	c.2991C>T	p.Pro997Pro	synonymous_variant	Exon 17 of 17		XP_047281723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6	c.2991C>T	p.Pro997Pro	synonymous_variant	Exon 17 of 17	5	NM_001195263.2	ENSP00000480489.1
PDZD7	ENST00000474125.7	n.*2938C>T		non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000474447.1
PDZD7	ENST00000474125.7	n.*2938C>T		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000474447.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000740 AC: 1 AN: 135074 AF XY: 0.0000136

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: 0.00

Gnomad NFE exome AF: 0.0000188

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000361 AC: 5 AN: 1383884 Hom.: 0 Cov.: 33 AF XY: 0.00000439 AC XY: 3 AN XY: 682860

African (AFR) AF: 0.00 AC: 0 AN: 31588

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1078878

Other (OTH) AF: 0.0000173 AC: 1 AN: 57902

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000508 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.76
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs1273046835; hg19: chr10-102768335;