chr8-492604-T-C

Position:

• chr8-492604-T-C

Variant summary

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

The NM_001384899.1(TDRP):​c.353A>G​(p.Asp118Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TDRP NM_001384899.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

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]

TDRP (HGNC:):

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=0.1708889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRP	NM_001384899.1	c.353A>G	p.Asp118Gly	missense_variant	3/3	ENST00000324079.11	NP_001371828.1
TDRP	NM_001256113.2	c.353A>G	p.Asp118Gly	missense_variant	3/4		NP_001243042.1
TDRP	NM_175075.5	c.353A>G	p.Asp118Gly	missense_variant	4/4		NP_778250.2
TDRP	XM_047421392.1	c.383A>G	p.Asp128Gly	missense_variant	4/4		XP_047277348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRP	ENST00000324079.11	c.353A>G	p.Asp118Gly	missense_variant	3/3	1	NM_001384899.1	ENSP00000315111.6
TDRP	ENST00000523656.5	c.353A>G	p.Asp118Gly	missense_variant	4/5	5		ENSP00000430325.1
TDRP	ENST00000524229.1	n.*26A>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461660 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

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

Jan 08, 2024

The c.353A>G (p.D118G) alteration is located in exon 3 (coding exon 3) of the TDRP gene. This alteration results from a A to G substitution at nucleotide position 353, causing the aspartic acid (D) at amino acid position 118 to be replaced by a glycine (G). 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	Benign	0.13
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.63	T;T;.;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.3	M;M;M;M
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.9	D;.;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D;.;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.97	.;D;D;.
Vest4		0.57
MutPred		0.26		Loss of stability (P = 0.0735);Loss of stability (P = 0.0735);Loss of stability (P = 0.0735);Loss of stability (P = 0.0735);
MVP		0.19
MPC		0.0077
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.69
gMVP		0.074

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1439590071; hg19: chr8-442604;