rs7853578

Variant names:

• chr9-97439269-A-G
• rs7853578
• NM_014290.3:c.588A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014290.3(TDRD7):​c.588A>G​(p.Gln196Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 1,601,674 control chromosomes in the GnomAD database, including 2,330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (625 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1705 hom.)
• Consequence: TDRD7 NM_014290.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.193
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-97439269-A-G is Benign according to our data. Variant chr9-97439269-A-G is described in ClinVar as Benign. ClinVar VariationId is 260384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.193 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD7	NM_014290.3	c.588A>G	p.Gln196Gln	synonymous_variant	Exon 5 of 17	ENST00000355295.5	NP_055105.2
TDRD7	NM_001302884.2	c.366A>G	p.Gln122Gln	synonymous_variant	Exon 4 of 16		NP_001289813.1
TDRD7	XM_047423111.1	c.588A>G	p.Gln196Gln	synonymous_variant	Exon 5 of 17		XP_047279067.1
TDRD7	XM_047423113.1	c.588A>G	p.Gln196Gln	synonymous_variant	Exon 5 of 14		XP_047279069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295.5	c.588A>G	p.Gln196Gln	synonymous_variant	Exon 5 of 17	1	NM_014290.3	ENSP00000347444.4

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10885 AN: 151748 Hom.: 614 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0367

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0759

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0560

GnomAD2 exomes AF: 0.0505 AC: 12344 AN: 244230 AF XY: 0.0500

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.0209

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.108

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0320

Gnomad OTH exome AF: 0.0391

GnomAD4 exome AF: 0.0391 AC: 56720 AN: 1449810 Hom.: 1705 Cov.: 32 AF XY: 0.0400 AC XY: 28862 AN XY: 721612

African (AFR) AF: 0.161 AC: 5348 AN: 33304

American (AMR) AF: 0.0225 AC: 1004 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 775 AN: 26086

East Asian (EAS) AF: 0.0849 AC: 3363 AN: 39634

South Asian (SAS) AF: 0.0778 AC: 6696 AN: 86014

European-Finnish (FIN) AF: 0.0337 AC: 1470 AN: 43654

Middle Eastern (MID) AF: 0.0424 AC: 244 AN: 5756

European-Non Finnish (NFE) AF: 0.0315 AC: 34963 AN: 1110510

Other (OTH) AF: 0.0475 AC: 2857 AN: 60196

GnomAD4 genome AF: 0.0720 AC: 10930 AN: 151864 Hom.: 625 Cov.: 32 AF XY: 0.0722 AC XY: 5358 AN XY: 74222

African (AFR) AF: 0.162 AC: 6691 AN: 41408

American (AMR) AF: 0.0367 AC: 559 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3470

East Asian (EAS) AF: 0.104 AC: 539 AN: 5174

South Asian (SAS) AF: 0.0762 AC: 367 AN: 4818

European-Finnish (FIN) AF: 0.0378 AC: 397 AN: 10510

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0315 AC: 2143 AN: 67940

Other (OTH) AF: 0.0569 AC: 120 AN: 2110

Alfa AF: 0.0531 Hom.: 118

Bravo AF: 0.0749

Asia WGS AF: 0.0830 AC: 287 AN: 3478

EpiCase AF: 0.0312

EpiControl AF: 0.0308

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cataract 36 Benign:2

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.

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

May 31, 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.

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.34
DANN	Benign	0.23
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7853578; hg19: chr9-100201551; COSMIC: COSV107439863;