chr9-97412112-C-G

Variant names:

• chr9-97412112-C-G
• rs10982012
• NM_014290.3:c.-133C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014290.3(TDRD7):​c.-133C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 152,826 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (108 hom., cov: 32)
  • Exomes 𝑓: 0.018 (1 hom.)
• Consequence: TDRD7 NM_014290.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.124
• 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

ENSG00000286375 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 9-97412112-C-G is Benign according to our data. Variant chr9-97412112-C-G is described in ClinVar as Benign. ClinVar VariationId is 364054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

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.-133C>G		5_prime_UTR	Exon 1 of 17	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.-142C>G		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.-133C>G		5_prime_UTR	Exon 1 of 17	ENSP00000347444.4	Q8NHU6-1
	TDRD7	ENST00000943579.1		c.-133C>G		5_prime_UTR	Exon 1 of 17	ENSP00000613638.1
	TDRD7	ENST00000943578.1		c.-133C>G		5_prime_UTR	Exon 1 of 16	ENSP00000613637.1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3735 AN: 151724 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00351

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.0181 AC: 18 AN: 994 Hom.: 1 Cov.: 0 AF XY: 0.0176 AC XY: 11 AN XY: 626

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.300 AC: 3 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.0833 AC: 1 AN: 12

South Asian (SAS) AF: 0.0267 AC: 13 AN: 486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00234 AC: 1 AN: 428

Other (OTH) AF: 0.00 AC: 0 AN: 40

GnomAD4 genome AF: 0.0246 AC: 3732 AN: 151832 Hom.: 108 Cov.: 32 AF XY: 0.0275 AC XY: 2042 AN XY: 74234

African (AFR) AF: 0.0288 AC: 1193 AN: 41474

American (AMR) AF: 0.0633 AC: 967 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.125 AC: 640 AN: 5140

South Asian (SAS) AF: 0.0325 AC: 157 AN: 4824

European-Finnish (FIN) AF: 0.0445 AC: 468 AN: 10518

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00351 AC: 238 AN: 67818

Other (OTH) AF: 0.0180 AC: 38 AN: 2106

Alfa AF: 0.00342 Hom.: 0

Bravo AF: 0.0281

Asia WGS AF: 0.0540 AC: 186 AN: 3440

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		0.12
PromoterAI		-0.037	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs10982012; hg19: chr9-100174394;