9-97412112-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014290.3(TDRD7):c.-133C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 152,826 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (108 hom., cov: 32)
  • Exomes 𝑓: 0.018 (1 hom.)
• Consequence: TDRD7 NM_014290.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.124

Genes affected

TDRD7 (HGNC:30831): (tudor domain containing 7) The protein encoded by this gene belongs to the Tudor family of proteins. This protein contains conserved Tudor domains and LOTUS domains. It is a component of RNA granules, which function in RNA processing. Mutations in this gene have been associated with cataract formation in mouse and human. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 9-97412112-C-G is Benign according to our data. Variant chr9-97412112-C-G is described in ClinVar as [Benign]. Clinvar id is 364054.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD7	NM_014290.3	c.-133C>G		5_prime_UTR_variant	1/17	ENST00000355295.5
TDRD7	NM_001302884.2	c.-142C>G		5_prime_UTR_variant	1/16
TDRD7	XM_047423113.1	c.-133C>G		5_prime_UTR_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD7	ENST00000355295.5	c.-133C>G		5_prime_UTR_variant	1/17	1	NM_014290.3	P1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3735 AN: 151724 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00351

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.0181 AC: 18 AN: 994 Hom.: 1 Cov.: 0 AF XY: 0.0176 AC XY: 11 AN XY: 626

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0833

Gnomad4 SAS exome AF: 0.0267

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00234

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0246 AC: 3732 AN: 151832 Hom.: 108 Cov.: 32 AF XY: 0.0275 AC XY: 2042 AN XY: 74234

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0445

Gnomad4 NFE AF: 0.00351

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00342 Hom.: 0

Bravo AF: 0.0281

Asia WGS AF: 0.0540 AC: 186 AN: 3440

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cataract 36 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	16
Dann	Benign	0.92

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: rs10982012; hg19: chr9-100174394;