9-97432124-T-C

Variant names:

• chr9-97432124-T-C
• rs2045732
• NM_014290.3:c.449T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0420
• Publications: 46 publications found

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)

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD7	NM_014290.3	c.449T>C	p.Val150Ala	missense_variant	Exon 4 of 17	ENST00000355295.5	NP_055105.2
TDRD7	NM_001302884.2	c.227T>C	p.Val76Ala	missense_variant	Exon 3 of 16		NP_001289813.1
TDRD7	XM_047423111.1	c.449T>C	p.Val150Ala	missense_variant	Exon 4 of 17		XP_047279067.1
TDRD7	XM_047423113.1	c.449T>C	p.Val150Ala	missense_variant	Exon 4 of 14		XP_047279069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295.5	c.449T>C	p.Val150Ala	missense_variant	Exon 4 of 17	1	NM_014290.3	ENSP00000347444.4

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80702 AN: 151888 Hom.: 21712 Cov.: 32

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

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.: 50 AF XY: 0.486 AC XY: 353347 AN XY: 727024

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

GnomAD4 genome AF: 0.532 AC: 80796 AN: 152006 Hom.: 21754 Cov.: 32 AF XY: 0.532 AC XY: 39485 AN XY: 74276

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

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

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cataract 36 Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.50
DEOGEN2	Benign	0.084	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.046	T
MetaRNN	Benign	0.000036	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.042
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.013
Sift	Benign	0.69	T
Sift4G	Benign	0.64	T
Polyphen		0.010	B
Vest4		0.0070
MPC		0.19
ClinPred		0.00087	T
GERP RS		1.0
Varity_R		0.015
gMVP		0.18
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2045732; hg19: chr9-100194406; COSMIC: COSV62428817;