9-97430831-T-C

Position:

• chr9-97430831-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014290.3(TDRD7):​c.208-102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,399,806 control chromosomes in the GnomAD database, including 143,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (15936 hom., cov: 32)
  • Exomes 𝑓: 0.45 (128017 hom.)
• Consequence: TDRD7 NM_014290.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.03

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-97430831-T-C is Benign according to our data. Variant chr9-97430831-T-C is described in ClinVar as [Benign]. Clinvar id is 1256911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD7	NM_014290.3	c.208-102T>C		intron_variant		ENST00000355295.5
TDRD7	NM_001302884.2	c.-15-102T>C		intron_variant
TDRD7	XM_047423111.1	c.208-102T>C		intron_variant
TDRD7	XM_047423113.1	c.208-102T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD7	ENST00000355295.5	c.208-102T>C		intron_variant		1	NM_014290.3	P1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69407 AN: 151878 Hom.: 15928 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.450 AC: 561955 AN: 1247810 Hom.: 128017 AF XY: 0.447 AC XY: 282147 AN XY: 631704

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.453

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.457 AC: 69452 AN: 151996 Hom.: 15936 Cov.: 32 AF XY: 0.457 AC XY: 33927 AN XY: 74294

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.463

Alfa AF: 0.449 Hom.: 3041

Bravo AF: 0.461

Asia WGS AF: 0.433 AC: 1508 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7874295; hg19: chr9-100193113; COSMIC: COSV62428808;