NM_014290.3:c.208-102T>C

Variant names:

• chr9-97430831-T-C
• rs7874295
• NM_014290.3:c.208-102T>C

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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.03
• Publications: 7 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=-0.82).
• BP6: Variant 9-97430831-T-C is Benign according to our data. Variant chr9-97430831-T-C is described in ClinVar as Benign. ClinVar VariationId is 1256911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.506 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.208-102T>C		intron	N/A	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.-15-102T>C		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.208-102T>C		intron	N/A	ENSP00000347444.4	Q8NHU6-1
	TDRD7	ENST00000861598.1		c.208-102T>C		intron	N/A	ENSP00000531657.1
	TDRD7	ENST00000861599.1		c.208-102T>C		intron	N/A	ENSP00000531658.1

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

African (AFR) AF: 0.438 AC: 12810 AN: 29228

American (AMR) AF: 0.556 AC: 24462 AN: 44000

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 10969 AN: 24698

East Asian (EAS) AF: 0.445 AC: 17194 AN: 38618

South Asian (SAS) AF: 0.360 AC: 29260 AN: 81324

European-Finnish (FIN) AF: 0.453 AC: 21588 AN: 47658

Middle Eastern (MID) AF: 0.360 AC: 1931 AN: 5360

European-Non Finnish (NFE) AF: 0.455 AC: 420177 AN: 923754

Other (OTH) AF: 0.443 AC: 23564 AN: 53170

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

African (AFR) AF: 0.440 AC: 18224 AN: 41420

American (AMR) AF: 0.515 AC: 7865 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1530 AN: 3470

East Asian (EAS) AF: 0.458 AC: 2363 AN: 5164

South Asian (SAS) AF: 0.360 AC: 1732 AN: 4814

European-Finnish (FIN) AF: 0.462 AC: 4881 AN: 10568

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31337 AN: 67976

Other (OTH) AF: 0.463 AC: 979 AN: 2114

Alfa AF: 0.457 Hom.: 8072

Bravo AF: 0.461

Asia WGS AF: 0.433 AC: 1508 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.62
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7874295; hg19: chr9-100193113; COSMIC: COSV62428808;