chr8-492725-C-G

Position:

• chr8-492725-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000324079.11(TDRP):​c.232G>C​(p.Glu78Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TDRP ENST00000324079.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.36

Genes affected

TDRP (HGNC:26951): (testis development related protein) Acts upstream of or within spermatogenesis. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18676773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRP	NM_001384899.1	c.232G>C	p.Glu78Gln	missense_variant	3/3	ENST00000324079.11	NP_001371828.1
TDRP	NM_001256113.2	c.232G>C	p.Glu78Gln	missense_variant	3/4		NP_001243042.1
TDRP	NM_175075.5	c.232G>C	p.Glu78Gln	missense_variant	4/4		NP_778250.2
TDRP	XM_047421392.1	c.262G>C	p.Glu88Gln	missense_variant	4/4		XP_047277348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRP	ENST00000324079.11	c.232G>C	p.Glu78Gln	missense_variant	3/3	1	NM_001384899.1	ENSP00000315111	P1
TDRP	ENST00000523656.5	c.232G>C	p.Glu78Gln	missense_variant	4/5	5		ENSP00000430325
TDRP	ENST00000524229.1	n.163G>C		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

The c.232G>C (p.E78Q) alteration is located in exon 3 (coding exon 3) of the TDRP gene. This alteration results from a G to C substitution at nucleotide position 232, causing the glutamic acid (E) at amino acid position 78 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T;T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;D;.;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.4	M;M;M;M
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.4	N;.;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0060	D;.;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.58
MutPred		0.20		Gain of MoRF binding (P = 0.0174);Gain of MoRF binding (P = 0.0174);Gain of MoRF binding (P = 0.0174);Gain of MoRF binding (P = 0.0174);
MVP		0.081
MPC		0.010
ClinPred		0.94	D
GERP RS		5.2
Varity_R		0.27
gMVP		0.093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-442725;