NM_014290.3:c.449T>G

Variant names:

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

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>G​(p.Val150Gly) 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: G2P, Labcorp Genetics (formerly Invitae)

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=0.077139944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRD7	NM_014290.3	c.449T>G	p.Val150Gly	missense_variant	Exon 4 of 17	ENST00000355295.5	NP_055105.2
TDRD7	NM_001302884.2	c.227T>G	p.Val76Gly	missense_variant	Exon 3 of 16		NP_001289813.1
TDRD7	XM_047423111.1	c.449T>G	p.Val150Gly	missense_variant	Exon 4 of 17		XP_047279067.1
TDRD7	XM_047423113.1	c.449T>G	p.Val150Gly	missense_variant	Exon 4 of 14		XP_047279069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRD7	ENST00000355295.5	c.449T>G	p.Val150Gly	missense_variant	Exon 4 of 17	1	NM_014290.3	ENSP00000347444.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 66001

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.1
DANN	Benign	0.58
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.042
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.011
Sift	Benign	0.33	T
Sift4G	Benign	0.39	T
Polyphen		0.023	B
Vest4		0.041
MutPred		0.37		Gain of sheet (P = 0.0028);
MVP		0.26
MPC		0.21
ClinPred		0.038	T
GERP RS		1.0
Varity_R		0.034
gMVP		0.29
Mutation Taster		=98/2	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;