rs7853578

Positions:

• chr9-97439269-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014290.3(TDRD7):​c.588A>G​(p.Gln196=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 260384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-97439269-A-G is described in Lovd as [Likely_benign].
• 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/exons	MANE	Protein	UniProt
TDRD7	NM_014290.3	c.588A>G	p.Gln196=	synonymous_variant	5/17	ENST00000355295.5	NP_055105.2
TDRD7	NM_001302884.2	c.366A>G	p.Gln122=	synonymous_variant	4/16		NP_001289813.1
TDRD7	XM_047423111.1	c.588A>G	p.Gln196=	synonymous_variant	5/17		XP_047279067.1
TDRD7	XM_047423113.1	c.588A>G	p.Gln196=	synonymous_variant	5/14		XP_047279069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295.5	c.588A>G	p.Gln196=	synonymous_variant	5/17	1	NM_014290.3	ENSP00000347444	P1

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

GnomAD3 exomes AF: 0.0505 AC: 12344 AN: 244230 Hom.: 566 AF XY: 0.0500 AC XY: 6630 AN XY: 132512

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 SAS exome AF: 0.0757

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

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.0225

Gnomad4 ASJ exome AF: 0.0297

Gnomad4 EAS exome AF: 0.0849

Gnomad4 SAS exome AF: 0.0778

Gnomad4 FIN exome AF: 0.0337

Gnomad4 NFE exome AF: 0.0315

Gnomad4 OTH exome AF: 0.0475

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

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0762

Gnomad4 FIN AF: 0.0378

Gnomad4 NFE AF: 0.0315

Gnomad4 OTH AF: 0.0569

Alfa AF: 0.0511 Hom.: 107

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

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 31, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.34
DANN	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs7853578; hg19: chr9-100201551;