rs1381532

Variant names:

• chr9-97428498-A-G
• rs1381532
• NM_014290.3:c.33A>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.33A>G​(p.Leu11Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,613,556 control chromosomes in the GnomAD database, including 197,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21774 hom., cov: 32)
  • Exomes 𝑓: 0.49 (175889 hom.)
• Consequence: TDRD7 NM_014290.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.52
• Publications: 26 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=-0.62).
• BP6: Variant 9-97428498-A-G is Benign according to our data. Variant chr9-97428498-A-G is described in ClinVar as Benign. ClinVar VariationId is 260382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.52 with no splicing effect.
• 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.33A>G	p.Leu11Leu	synonymous_variant	Exon 2 of 17	ENST00000355295.5	NP_055105.2
TDRD7	XM_047423111.1	c.33A>G	p.Leu11Leu	synonymous_variant	Exon 2 of 17		XP_047279067.1
TDRD7	XM_047423113.1	c.33A>G	p.Leu11Leu	synonymous_variant	Exon 2 of 14		XP_047279069.1
TDRD7	NM_001302884.2	c.-15-2435A>G		intron_variant	Intron 1 of 15		NP_001289813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295.5	c.33A>G	p.Leu11Leu	synonymous_variant	Exon 2 of 17	1	NM_014290.3	ENSP00000347444.4

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80740 AN: 151930 Hom.: 21732 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.523

GnomAD2 exomes AF: 0.508 AC: 127526 AN: 251002 AF XY: 0.499

Gnomad AFR exome AF: 0.608

Gnomad AMR exome AF: 0.582

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.562

Gnomad FIN exome AF: 0.486

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.487

GnomAD4 exome AF: 0.489 AC: 714018 AN: 1461508 Hom.: 175889 Cov.: 59 AF XY: 0.486 AC XY: 353490 AN XY: 727076

African (AFR) AF: 0.608 AC: 20359 AN: 33462

American (AMR) AF: 0.579 AC: 25865 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 12358 AN: 26124

East Asian (EAS) AF: 0.531 AC: 21071 AN: 39696

South Asian (SAS) AF: 0.438 AC: 37764 AN: 86254

European-Finnish (FIN) AF: 0.482 AC: 25767 AN: 53406

Middle Eastern (MID) AF: 0.405 AC: 2325 AN: 5744

European-Non Finnish (NFE) AF: 0.485 AC: 538952 AN: 1111756

Other (OTH) AF: 0.490 AC: 29557 AN: 60374

GnomAD4 genome AF: 0.532 AC: 80834 AN: 152048 Hom.: 21774 Cov.: 32 AF XY: 0.532 AC XY: 39504 AN XY: 74312

African (AFR) AF: 0.612 AC: 25378 AN: 41476

American (AMR) AF: 0.555 AC: 8479 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1638 AN: 3466

East Asian (EAS) AF: 0.561 AC: 2897 AN: 5166

South Asian (SAS) AF: 0.437 AC: 2103 AN: 4816

European-Finnish (FIN) AF: 0.495 AC: 5228 AN: 10558

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33461 AN: 67968

Other (OTH) AF: 0.523 AC: 1103 AN: 2110

Alfa AF: 0.501 Hom.: 25105

Bravo AF: 0.540

Asia WGS AF: 0.513 AC: 1784 AN: 3478

EpiCase AF: 0.476

EpiControl AF: 0.480

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

- -

Jan 13, 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. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

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. -

-

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	-0.62
CADD	Benign	0.83
DANN	Benign	0.74
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	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: rs1381532; hg19: chr9-100190780; COSMIC: COSV62428704;