rs2045732

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.449T>C(p.Val150Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 1,613,408 control chromosomes in the GnomAD database, including 197,486 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21754 hom., cov: 32)

Exomes 𝑓: 0.49 ( 175732 hom. )

Consequence

TDRD7
NM_014290.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0420

Publications

46 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 (MetaRNN=3.607712E-5).

BP6

Variant 9-97432124-T-C is Benign according to our data. Variant chr9-97432124-T-C is described in ClinVar as Benign. ClinVar VariationId is 260383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 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.449T>C	p.Val150Ala	missense	Exon 4 of 17	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.227T>C	p.Val76Ala	missense	Exon 3 of 16	NP_001289813.1	Q8NHU6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TDRD7	ENST00000355295.5	TSL:1 MANE Select	c.449T>C	p.Val150Ala	missense	Exon 4 of 17	ENSP00000347444.4	Q8NHU6-1
TDRD7	ENST00000861598.1		c.449T>C	p.Val150Ala	missense	Exon 5 of 18	ENSP00000531657.1
TDRD7	ENST00000861599.1		c.449T>C	p.Val150Ala	missense	Exon 4 of 17	ENSP00000531658.1

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80702

AN:

151888

Hom.:

21712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.611

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.554

Gnomad ASJ

AF:

0.472

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.523

GnomAD2 exomes

AF:

0.508

AC:

127446

AN:

250900

AF XY:

0.499

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.581

Gnomad ASJ exome

AF:

0.478

Gnomad EAS exome

AF:

0.561

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.487

GnomAD4 exome

AF:

0.488

AC:

713659

AN:

1461402

Hom.:

175732

Cov.:

AF XY:

0.486

AC XY:

353347

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.608

AC:

20340

AN:

33446

American (AMR)

AF:

0.578

AC:

25837

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

12350

AN:

26122

East Asian (EAS)

AF:

0.530

AC:

21021

AN:

39692

South Asian (SAS)

AF:

0.438

AC:

37794

AN:

86254

European-Finnish (FIN)

AF:

0.483

AC:

25773

AN:

53414

Middle Eastern (MID)

AF:

0.402

AC:

2319

AN:

5764

European-Non Finnish (NFE)

AF:

0.485

AC:

538704

AN:

1111674

Other (OTH)

AF:

0.489

AC:

29521

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

22242

44485

66727

88970

111212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15850

31700

47550

63400

79250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.532

AC:

80796

AN:

152006

Hom.:

21754

Cov.:

AF XY:

0.532

AC XY:

39485

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.612

AC:

25363

AN:

41448

American (AMR)

AF:

0.555

AC:

8473

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

1637

AN:

3470

East Asian (EAS)

AF:

0.560

AC:

2894

AN:

5172

South Asian (SAS)

AF:

0.437

AC:

2110

AN:

4826

European-Finnish (FIN)

AF:

0.495

AC:

5231

AN:

10558

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.492

AC:

33436

AN:

67936

Other (OTH)

AF:

0.522

AC:

1105

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1918

3836

5753

7671

9589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.503

Hom.:

66001

Bravo

AF:

0.540

TwinsUK

AF:

0.476

AC:

1765

ALSPAC

AF:

0.487

AC:

1878

ESP6500AA

AF:

0.605

AC:

2664

ESP6500EA

AF:

0.475

AC:

4088

ExAC

AF:

0.507

AC:

61557

Asia WGS

AF:

0.512

AC:

1781

AN:

3476

EpiCase

AF:

0.475

EpiControl

AF:

0.479

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 36 (3)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.0

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.084

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.046

MetaRNN

Benign

0.000036

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.69

PhyloP100

0.042

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.080

REVEL

Benign

0.013

Sift

Benign

0.69

Sift4G

Benign

0.64

Polyphen

0.010

Vest4

0.0070

MPC

0.19

ClinPred

0.00087

GERP RS

1.0

Varity_R

0.015

gMVP

0.18

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over