rs10817568

Variant names:

• chr9-97428690-C-T
• rs10817568
• NM_014290.3:c.207+18C>T

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.213
• Publications: 1 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014290.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD7	NM_014290.3	MANE Select	c.207+18C>T		intron	N/A	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.-15-2243C>T		intron	N/A	NP_001289813.1	Q8NHU6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD7	ENST00000355295.5	TSL:1 MANE Select	c.207+18C>T		intron	N/A	ENSP00000347444.4	Q8NHU6-1
	TDRD7	ENST00000861598.1		c.207+18C>T		intron	N/A	ENSP00000531657.1
	TDRD7	ENST00000861599.1		c.207+18C>T		intron	N/A	ENSP00000531658.1

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

GnomAD2 exomes AF: 0.0347 AC: 8638 AN: 248698 AF XY: 0.0308

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 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

African (AFR) AF: 0.0256 AC: 854 AN: 33380

American (AMR) AF: 0.103 AC: 4579 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00280 AC: 73 AN: 26110

East Asian (EAS) AF: 0.125 AC: 4964 AN: 39674

South Asian (SAS) AF: 0.0308 AC: 2657 AN: 86194

European-Finnish (FIN) AF: 0.0442 AC: 2275 AN: 51432

Middle Eastern (MID) AF: 0.0115 AC: 65 AN: 5644

European-Non Finnish (NFE) AF: 0.00289 AC: 3209 AN: 1109420

Other (OTH) AF: 0.0150 AC: 905 AN: 60248

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

African (AFR) AF: 0.0244 AC: 1012 AN: 41556

American (AMR) AF: 0.0621 AC: 949 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.116 AC: 598 AN: 5166

South Asian (SAS) AF: 0.0326 AC: 157 AN: 4820

European-Finnish (FIN) AF: 0.0442 AC: 468 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00353 AC: 240 AN: 68020

Other (OTH) AF: 0.0170 AC: 36 AN: 2114

Alfa AF: 0.0110 Hom.: 6

Bravo AF: 0.0257

Asia WGS AF: 0.0610 AC: 210 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cataract 36 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		-0.21
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: rs10817568; hg19: chr9-100190972;