rs12552100

Variant names:

• chr9-97472351-T-C
• rs12552100
• NM_014290.3:c.1800T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014290.3(TDRD7):​c.1800T>C​(p.Cys600Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00925 in 1,613,996 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0095 (85 hom.)
• Consequence: TDRD7 NM_014290.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.555
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 9-97472351-T-C is Benign according to our data. Variant chr9-97472351-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.555 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0073 (1112/152308) while in subpopulation NFE AF = 0.0101 (690/68014). AF 95% confidence interval is 0.00952. There are 10 homozygotes in GnomAd4. There are 546 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 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.1800T>C	p.Cys600Cys	synonymous	Exon 10 of 17	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.1578T>C	p.Cys526Cys	synonymous	Exon 9 of 16	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.1800T>C	p.Cys600Cys	synonymous	Exon 10 of 17	ENSP00000347444.4	Q8NHU6-1
	TDRD7	ENST00000861598.1		c.1800T>C	p.Cys600Cys	synonymous	Exon 11 of 18	ENSP00000531657.1
	TDRD7	ENST00000861599.1		c.1788T>C	p.Cys596Cys	synonymous	Exon 10 of 17	ENSP00000531658.1

Frequencies

GnomAD3 genomes AF: 0.00731 AC: 1112 AN: 152190 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.00634 AC: 1593 AN: 251126 AF XY: 0.00634

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0168

Gnomad NFE exome AF: 0.00925

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00946 AC: 13821 AN: 1461688 Hom.: 85 Cov.: 32 AF XY: 0.00926 AC XY: 6737 AN XY: 727152

African (AFR) AF: 0.00137 AC: 46 AN: 33466

American (AMR) AF: 0.00273 AC: 122 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00176 AC: 46 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.0183 AC: 977 AN: 53418

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.0109 AC: 12165 AN: 1111870

Other (OTH) AF: 0.00752 AC: 454 AN: 60390

GnomAD4 genome AF: 0.00730 AC: 1112 AN: 152308 Hom.: 10 Cov.: 32 AF XY: 0.00733 AC XY: 546 AN XY: 74482

African (AFR) AF: 0.00180 AC: 75 AN: 41578

American (AMR) AF: 0.00242 AC: 37 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0213 AC: 226 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0101 AC: 690 AN: 68014

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00846 Hom.: 16

Bravo AF: 0.00603

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00949

EpiControl AF: 0.00966

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Cataract 36 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.7
DANN	Benign	0.69
PhyloP100		0.56
Mutation Taster		=299/1	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: rs12552100; hg19: chr9-100234633; COSMIC: COSV108199428;