rs151288166

Variant names:

• chr9-97465035-A-G
• rs151288166
• NM_014290.3:c.1629+7A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014290.3(TDRD7):​c.1629+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,612,878 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00095 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (50 hom.)
• Consequence: TDRD7 NM_014290.3 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.861
• Publications: 2 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=-0.84).
• BP6: Variant 9-97465035-A-G is Benign according to our data. Variant chr9-97465035-A-G is described in ClinVar as Benign. ClinVar VariationId is 260376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000952 (145/152342) while in subpopulation SAS AF = 0.0222 (107/4828). AF 95% confidence interval is 0.0188. There are 3 homozygotes in GnomAd4. There are 96 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.1629+7A>G		splice_region intron	N/A	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.1407+7A>G		splice_region 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.1629+7A>G		splice_region intron	N/A	ENSP00000347444.4	Q8NHU6-1
	TDRD7	ENST00000861598.1		c.1629+7A>G		splice_region intron	N/A	ENSP00000531657.1
	TDRD7	ENST00000861599.1		c.1629+7A>G		splice_region intron	N/A	ENSP00000531658.1

Frequencies

GnomAD3 genomes AF: 0.000953 AC: 145 AN: 152224 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00261 AC: 647 AN: 248270 AF XY: 0.00343

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000999

Gnomad EAS exome AF: 0.00111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000894

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00182 AC: 2663 AN: 1460536 Hom.: 50 Cov.: 32 AF XY: 0.00235 AC XY: 1710 AN XY: 726512

African (AFR) AF: 0.000150 AC: 5 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00149 AC: 39 AN: 26104

East Asian (EAS) AF: 0.0190 AC: 752 AN: 39540

South Asian (SAS) AF: 0.0199 AC: 1710 AN: 86074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1111354

Other (OTH) AF: 0.00159 AC: 96 AN: 60324

GnomAD4 genome AF: 0.000952 AC: 145 AN: 152342 Hom.: 3 Cov.: 33 AF XY: 0.00129 AC XY: 96 AN XY: 74494

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5182

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.000253

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.55
PhyloP100		0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs151288166; hg19: chr9-100227317;