rs1381532

Positions:

chr9-97428498-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000355295.5(TDRD7):c.33A>G(p.Leu11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,613,556 control chromosomes in the GnomAD database, including 197,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21774 hom., cov: 32)

Exomes 𝑓: 0.49 ( 175889 hom. )

Consequence

TDRD7
ENST00000355295.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.52

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 9-97428498-A-G is Benign according to our data. Variant chr9-97428498-A-G is described in ClinVar as [Benign]. Clinvar id is 260382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-97428498-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TDRD7	NM_014290.3 linkuse as main transcript	c.33A>G	p.Leu11=	synonymous_variant	2/17	ENST00000355295.5	NP_055105.2
TDRD7	XM_047423111.1 linkuse as main transcript	c.33A>G	p.Leu11=	synonymous_variant	2/17		XP_047279067.1
TDRD7	XM_047423113.1 linkuse as main transcript	c.33A>G	p.Leu11=	synonymous_variant	2/14		XP_047279069.1
TDRD7	NM_001302884.2 linkuse as main transcript	c.-15-2435A>G		intron_variant			NP_001289813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295.5 linkuse as main transcript	c.33A>G	p.Leu11=	synonymous_variant	2/17	1	NM_014290.3	ENSP00000347444	P1	Q8NHU6-1

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80740

AN:

151930

Hom.:

21732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.611

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.554

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.562

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.523

GnomAD3 exomes

AF:

0.508

AC:

127526

AN:

251002

Hom.:

32937

AF XY:

0.499

AC XY:

67701

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.582

Gnomad ASJ exome

AF:

0.477

Gnomad EAS exome

AF:

0.562

Gnomad SAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.487

GnomAD4 exome

AF:

0.489

AC:

714018

AN:

1461508

Hom.:

175889

Cov.:

AF XY:

0.486

AC XY:

353490

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.608

Gnomad4 AMR exome

AF:

0.579

Gnomad4 ASJ exome

AF:

0.473

Gnomad4 EAS exome

AF:

0.531

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.482

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.490

GnomAD4 genome

AF:

0.532

AC:

80834

AN:

152048

Hom.:

21774

Cov.:

AF XY:

0.532

AC XY:

39504

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.612

Gnomad4 AMR

AF:

0.555

Gnomad4 ASJ

AF:

0.473

Gnomad4 EAS

AF:

0.561

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.495

Gnomad4 NFE

AF:

0.492

Gnomad4 OTH

AF:

0.523

Alfa

AF:

0.498

Hom.:

19556

Bravo

AF:

0.540

Asia WGS

AF:

0.513

AC:

1784

AN:

3478

EpiCase

AF:

0.476

EpiControl

AF:

0.480

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 36

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
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:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.83

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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