rs12552100

Positions:

• chr9-97472351-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014290.3(TDRD7):​c.1800T>C​(p.Cys600=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00925 in 1,613,996 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0095 (85 hom.)
• Consequence: TDRD7 NM_014290.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.555

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=-0.52).
• BP6: Variant 9-97472351-T-C is Benign according to our data. Variant chr9-97472351-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 260377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-97472351-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.555 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0073 (1112/152308) while in subpopulation NFE AF= 0.0101 (690/68014). AF 95% confidence interval is 0.00952. There are 10 homozygotes in gnomad4. There are 546 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD7	NM_014290.3	c.1800T>C	p.Cys600=	synonymous_variant	10/17	ENST00000355295.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD7	ENST00000355295.5	c.1800T>C	p.Cys600=	synonymous_variant	10/17	1	NM_014290.3	P1

Frequencies

GnomAD3 genomes AF: 0.00731 AC: 1112 AN: 152190 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00634 AC: 1593 AN: 251126 Hom.: 8 AF XY: 0.00634 AC XY: 860 AN XY: 135694

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0168

Gnomad NFE exome AF: 0.00925

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00946 AC: 13821 AN: 1461688 Hom.: 85 Cov.: 32 AF XY: 0.00926 AC XY: 6737 AN XY: 727152

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.00273

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0183

Gnomad4 NFE exome AF: 0.0109

Gnomad4 OTH exome AF: 0.00752

GnomAD4 genome AF: 0.00730 AC: 1112 AN: 152308 Hom.: 10 Cov.: 32 AF XY: 0.00733 AC XY: 546 AN XY: 74482

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0213

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00742 Hom.: 5

Bravo AF: 0.00603

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00949

EpiControl AF: 0.00966

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 09, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	TDRD7: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cataract 36 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

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	-0.52
CADD	Benign	7.7
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs12552100; hg19: chr9-100234633;