rs749676206

Variant names:

• chr9-97428519-T-C
• rs749676206
• NM_014290.3:c.54T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP7 BS1_Supporting

The NM_014290.3(TDRD7):​c.54T>C​(p.His18His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: TDRD7 NM_014290.3 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.783
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.783 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000157 (23/1461732) while in subpopulation SAS AF = 0.00022 (19/86258). AF 95% confidence interval is 0.000143. There are 0 homozygotes in GnomAdExome4. There are 18 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.54T>C	p.His18His	synonymous	Exon 2 of 17	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.-15-2414T>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.54T>C	p.His18His	synonymous	Exon 2 of 17	ENSP00000347444.4	Q8NHU6-1
	TDRD7	ENST00000861598.1		c.54T>C	p.His18His	synonymous	Exon 3 of 18	ENSP00000531657.1
	TDRD7	ENST00000861599.1		c.54T>C	p.His18His	synonymous	Exon 2 of 17	ENSP00000531658.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251202 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461732 Hom.: 0 Cov.: 34 AF XY: 0.0000248 AC XY: 18 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111920

Other (OTH) AF: 0.0000662 AC: 4 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cataract 36 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.4
DANN	Benign	0.63
PhyloP100		0.78
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: rs749676206; hg19: chr9-100190801;