9-97432124-T-A

Variant names:

• chr9-97432124-T-A
• rs2045732
• NM_014290.3:c.449T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014290.3(TDRD7):​c.449T>A​(p.Val150Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V150A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TDRD7 NM_014290.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 46 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08688703).

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.449T>A	p.Val150Asp	missense	Exon 4 of 17	NP_055105.2	Q8NHU6-1
	TDRD7	NM_001302884.2		c.227T>A	p.Val76Asp	missense	Exon 3 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.449T>A	p.Val150Asp	missense	Exon 4 of 17	ENSP00000347444.4	Q8NHU6-1
	TDRD7	ENST00000861598.1		c.449T>A	p.Val150Asp	missense	Exon 5 of 18	ENSP00000531657.1
	TDRD7	ENST00000861599.1		c.449T>A	p.Val150Asp	missense	Exon 4 of 17	ENSP00000531658.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.8
DANN	Benign	0.74
DEOGEN2	Benign	0.097	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.042
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.010
Sift	Benign	0.21	T
Sift4G	Benign	0.30	T
Polyphen		0.055	B
Vest4		0.11
MutPred		0.39		Gain of sheet (P = 0.0061)
MVP		0.25
MPC		0.26
ClinPred		0.031	T
GERP RS		1.0
Varity_R		0.049
gMVP		0.33
Mutation Taster		=93/7	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: rs2045732; hg19: chr9-100194406;