Variant 9-97412112-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.124

Variant links:

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]

TDRD7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
TDRD7	NM_014290.3 linkuse as main transcript	c.-133C>G	5_prime_UTR_variant	1/17	ENST00000355295.5	NP_055105.2	Q8NHU6-1
TDRD7	NM_001302884.2 linkuse as main transcript	c.-142C>G	5_prime_UTR_variant	1/16		NP_001289813.1	Q8NHU6-2
TDRD7	XM_047423113.1 linkuse as main transcript	c.-133C>G	5_prime_UTR_variant	1/14		XP_047279069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295 linkuse as main transcript	c.-133C>G		5_prime_UTR_variant	1/17	1	NM_014290.3	ENSP00000347444.4		Q8NHU6-1

Frequencies

GnomAD3 genomes

AF:

0.0246

AC:

3735

AN:

151724

Hom.:

108

Cov.:

show subpopulations

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:

AN:

994

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

AN XY:

626

show subpopulations

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.:

AF XY:

0.0275

AC XY:

2042

AN XY:

74234

show subpopulations

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.:

Bravo

AF:

0.0281

Asia WGS

AF:

0.0540

AC:

186

AN:

3440

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over