9-97412162-G-C

Variant names:

• chr9-97412162-G-C
• rs373486700
• NM_014290.3:c.-83G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014290.3(TDRD7):​c.-83G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 154,410 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (0 hom.)
• Consequence: TDRD7 NM_014290.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00
• 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

ENSG00000286375 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00423 (644/152150) while in subpopulation EAS AF = 0.0285 (147/5160). AF 95% confidence interval is 0.0247. There are 9 homozygotes in GnomAd4. There are 438 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 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.-83G>C		5_prime_UTR	Exon 1 of 17	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.-92G>C		5_prime_UTR	Exon 1 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.-83G>C		5_prime_UTR	Exon 1 of 17	ENSP00000347444.4	Q8NHU6-1
	TDRD7	ENST00000861598.1		c.-160G>C		5_prime_UTR	Exon 1 of 18	ENSP00000531657.1
	TDRD7	ENST00000861599.1		c.-83G>C		5_prime_UTR	Exon 1 of 17	ENSP00000531658.1

Frequencies

GnomAD3 genomes AF: 0.00426 AC: 647 AN: 152042 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.0288

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.00221 AC: 5 AN: 2260 Hom.: 0 Cov.: 0 AF XY: 0.000602 AC XY: 1 AN XY: 1662

African (AFR) AF: 0.00 AC: 0 AN: 22

American (AMR) AF: 0.00 AC: 0 AN: 32

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20

East Asian (EAS) AF: 0.0303 AC: 2 AN: 66

South Asian (SAS) AF: 0.00 AC: 0 AN: 322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.00178 AC: 3 AN: 1686

Other (OTH) AF: 0.00 AC: 0 AN: 84

GnomAD4 genome AF: 0.00423 AC: 644 AN: 152150 Hom.: 9 Cov.: 32 AF XY: 0.00589 AC XY: 438 AN XY: 74398

African (AFR) AF: 0.0000481 AC: 2 AN: 41554

American (AMR) AF: 0.000327 AC: 5 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.0285 AC: 147 AN: 5160

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.0377 AC: 399 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00115 AC: 78 AN: 67954

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00281 Hom.: 0

Bravo AF: 0.00138

Asia WGS AF: 0.00994 AC: 34 AN: 3432

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	-0.56
CADD	Benign	14
DANN	Benign	0.86
PhyloP100		3.0
PromoterAI		-0.00010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=296/4	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: rs373486700; hg19: chr9-100174444;