Genetic Variant TDRD7:c.207+169T>C (chr9-97428841-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014290.3(TDRD7):c.207+169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,114 control chromosomes in the GnomAD database, including 15,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 15904 hom., cov: 33)

Consequence

TDRD7
NM_014290.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0520

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

cataract 36
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

TDRD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 9-97428841-T-C is Benign according to our data. Variant chr9-97428841-T-C is described in ClinVar as Benign. ClinVar VariationId is 1260120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014290.3. 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
	TDRD7	NM_014290.3	MANE Select	c.207+169T>C		intron	N/A	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.-15-2092T>C		intron	N/A	NP_001289813.1	Q8NHU6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TDRD7	ENST00000355295.5	TSL:1 MANE Select	c.207+169T>C	intron	N/A	ENSP00000347444.4	Q8NHU6-1
TDRD7	ENST00000861598.1		c.207+169T>C	intron	N/A	ENSP00000531657.1
TDRD7	ENST00000861599.1		c.207+169T>C	intron	N/A	ENSP00000531658.1

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69345

AN:

151996

Hom.:

15898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.439

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.463

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.456

AC:

69383

AN:

152114

Hom.:

15904

Cov.:

AF XY:

0.456

AC XY:

33891

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.439

AC:

18213

AN:

41474

American (AMR)

AF:

0.515

AC:

7879

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

1531

AN:

3472

East Asian (EAS)

AF:

0.457

AC:

2371

AN:

5184

South Asian (SAS)

AF:

0.359

AC:

1733

AN:

4826

European-Finnish (FIN)

AF:

0.457

AC:

4833

AN:

10574

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.461

AC:

31306

AN:

67980

Other (OTH)

AF:

0.462

AC:

976

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1991

3982

5973

7964

9955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

628

1256

1884

2512

3140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.452

Hom.:

1974

Bravo

AF:

0.461

Asia WGS

AF:

0.429

AC:

1493

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

(source)

DANN

Benign

0.79

PhyloP100

-0.052

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over