Genetic Variant TDRD7:p.Lys641Asn (chr9-97472474-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014290.3(TDRD7):c.1923G>C(p.Lys641Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K641K) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TDRD7
NM_014290.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

Publications

0 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: G2P, Labcorp Genetics (formerly Invitae)

TDRD7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36496437).

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.1923G>C	p.Lys641Asn	missense	Exon 10 of 17	NP_055105.2
	TDRD7	NM_001302884.2		c.1701G>C	p.Lys567Asn	missense	Exon 9 of 16	NP_001289813.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TDRD7	ENST00000355295.5	TSL:1 MANE Select	c.1923G>C	p.Lys641Asn	missense	Exon 10 of 17	ENSP00000347444.4
TDRD7	ENST00000861598.1		c.1923G>C	p.Lys641Asn	missense	Exon 11 of 18	ENSP00000531657.1
TDRD7	ENST00000861599.1		c.1911G>C	p.Lys637Asn	missense	Exon 10 of 17	ENSP00000531658.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461380

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111706

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Benign

0.012

MetaRNN

Benign

0.36

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

1.3

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.0

REVEL

Benign

0.10

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.010

Polyphen

0.95

Vest4

0.45

MutPred

0.45

Loss of ubiquitination at K641 (P = 0.0107)

MVP

0.40

MPC

0.28

ClinPred

0.53

GERP RS

0.19

Varity_R

0.11

gMVP

0.60

Mutation Taster

=78/22

polymorphism

(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