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 -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting 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 -9 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. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• 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;