9-97428690-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014290.3(TDRD7):c.207+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,609,000 control chromosomes in the GnomAD database, including 811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (97 hom., cov: 32)
  • Exomes 𝑓: 0.013 (714 hom.)
• Consequence: TDRD7 NM_014290.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.213

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 9-97428690-C-T is Benign according to our data. Variant chr9-97428690-C-T is described in ClinVar as [Benign]. Clinvar id is 260379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD7	NM_014290.3	c.207+18C>T		intron_variant		ENST00000355295.5
TDRD7	NM_001302884.2	c.-15-2243C>T		intron_variant
TDRD7	XM_047423111.1	c.207+18C>T		intron_variant
TDRD7	XM_047423113.1	c.207+18C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD7	ENST00000355295.5	c.207+18C>T		intron_variant		1	NM_014290.3	P1

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3471 AN: 152112 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00353

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.0347 AC: 8638 AN: 248698 Hom.: 370 AF XY: 0.0308 AC XY: 4151 AN XY: 134610

Gnomad AFR exome AF: 0.0257

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.111

Gnomad SAS exome AF: 0.0307

Gnomad FIN exome AF: 0.0432

Gnomad NFE exome AF: 0.00442

Gnomad OTH exome AF: 0.0233

GnomAD4 exome AF: 0.0134 AC: 19581 AN: 1456770 Hom.: 714 Cov.: 32 AF XY: 0.0134 AC XY: 9689 AN XY: 724958

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.00280

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.0308

Gnomad4 FIN exome AF: 0.0442

Gnomad4 NFE exome AF: 0.00289

Gnomad4 OTH exome AF: 0.0150

GnomAD4 genome AF: 0.0228 AC: 3470 AN: 152230 Hom.: 97 Cov.: 32 AF XY: 0.0258 AC XY: 1921 AN XY: 74422

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.0621

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0326

Gnomad4 FIN AF: 0.0442

Gnomad4 NFE AF: 0.00353

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0101 Hom.: 2

Bravo AF: 0.0257

Asia WGS AF: 0.0610 AC: 210 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Cataract 36 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	13
Dann	Benign	0.78

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: rs10817568; hg19: chr9-100190972;