rs41281938

Positions:

• chr9-97472474-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014290.3(TDRD7):​c.1923G>A​(p.Lys641=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 1,613,386 control chromosomes in the GnomAD database, including 1,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (198 hom., cov: 32)
  • Exomes 𝑓: 0.030 (872 hom.)
• Consequence: TDRD7 NM_014290.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.35

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 9-97472474-G-A is Benign according to our data. Variant chr9-97472474-G-A is described in ClinVar as [Benign]. Clinvar id is 364071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD7	NM_014290.3	c.1923G>A	p.Lys641=	synonymous_variant	10/17	ENST00000355295.5	NP_055105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295.5	c.1923G>A	p.Lys641=	synonymous_variant	10/17	1	NM_014290.3	ENSP00000347444	P1

Frequencies

GnomAD3 genomes AF: 0.0441 AC: 6702 AN: 152062 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0368

GnomAD3 exomes AF: 0.0288 AC: 7168 AN: 249128 Hom.: 172 AF XY: 0.0287 AC XY: 3873 AN XY: 134790

Gnomad AFR exome AF: 0.0938

Gnomad AMR exome AF: 0.0157

Gnomad ASJ exome AF: 0.0219

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0331

Gnomad FIN exome AF: 0.0144

Gnomad NFE exome AF: 0.0304

Gnomad OTH exome AF: 0.0269

GnomAD4 exome AF: 0.0304 AC: 44417 AN: 1461206 Hom.: 872 Cov.: 31 AF XY: 0.0306 AC XY: 22212 AN XY: 726920

Gnomad4 AFR exome AF: 0.0918

Gnomad4 AMR exome AF: 0.0166

Gnomad4 ASJ exome AF: 0.0222

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0349

Gnomad4 FIN exome AF: 0.0140

Gnomad4 NFE exome AF: 0.0308

Gnomad4 OTH exome AF: 0.0302

GnomAD4 genome AF: 0.0440 AC: 6701 AN: 152180 Hom.: 198 Cov.: 32 AF XY: 0.0424 AC XY: 3156 AN XY: 74416

Gnomad4 AFR AF: 0.0903

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.0134

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0364

Alfa AF: 0.0354 Hom.: 77

Bravo AF: 0.0464

Asia WGS AF: 0.0130 AC: 47 AN: 3478

EpiCase AF: 0.0309

EpiControl AF: 0.0294

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cataract 36 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
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 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

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	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.6
DANN	Benign	0.64

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: rs41281938; hg19: chr9-100234756;