rs13286028

Variant names:

• chr9-97430704-T-C
• rs13286028
• NM_014290.3:c.208-229T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014290.3(TDRD7):​c.208-229T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,156 control chromosomes in the GnomAD database, including 4,771 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (4771 hom., cov: 32)
• Consequence: TDRD7 NM_014290.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.493
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 9-97430704-T-C is Benign according to our data. Variant chr9-97430704-T-C is described in ClinVar as Benign. ClinVar VariationId is 1238760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD7	NM_014290.3	c.208-229T>C		intron_variant	Intron 2 of 16	ENST00000355295.5	NP_055105.2
TDRD7	NM_001302884.2	c.-15-229T>C		intron_variant	Intron 1 of 15		NP_001289813.1
TDRD7	XM_047423111.1	c.208-229T>C		intron_variant	Intron 2 of 16		XP_047279067.1
TDRD7	XM_047423113.1	c.208-229T>C		intron_variant	Intron 2 of 13		XP_047279069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295.5	c.208-229T>C		intron_variant	Intron 2 of 16	1	NM_014290.3	ENSP00000347444.4

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37563 AN: 152038 Hom.: 4775 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37555 AN: 152156 Hom.: 4771 Cov.: 32 AF XY: 0.244 AC XY: 18184 AN XY: 74376

African (AFR) AF: 0.214 AC: 8900 AN: 41544

American (AMR) AF: 0.236 AC: 3614 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3466

East Asian (EAS) AF: 0.178 AC: 919 AN: 5174

South Asian (SAS) AF: 0.183 AC: 883 AN: 4820

European-Finnish (FIN) AF: 0.238 AC: 2514 AN: 10576

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18589 AN: 67982

Other (OTH) AF: 0.258 AC: 543 AN: 2108

Alfa AF: 0.268 Hom.: 9374

Bravo AF: 0.246

Asia WGS AF: 0.192 AC: 673 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 28, 2018

GeneDx

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	-0.69
CADD	Benign	9.6
DANN	Benign	0.89
PhyloP100		0.49
Mutation Taster		=100/0	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: rs13286028; hg19: chr9-100192986;