8-494582-A-C

Position:

• chr8-494582-A-C

Variant summary

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

The NM_001384899.1(TDRP):​c.124T>G​(p.Phe42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TDRP NM_001384899.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRP	NM_001384899.1	c.124T>G	p.Phe42Val	missense_variant	2/3	ENST00000324079.11	NP_001371828.1
TDRP	NM_001256113.2	c.124T>G	p.Phe42Val	missense_variant	2/4		NP_001243042.1
TDRP	NM_175075.5	c.124T>G	p.Phe42Val	missense_variant	3/4		NP_778250.2
TDRP	XM_047421392.1	c.154T>G	p.Phe52Val	missense_variant	3/4		XP_047277348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRP	ENST00000324079.11	c.124T>G	p.Phe42Val	missense_variant	2/3	1	NM_001384899.1	ENSP00000315111.6
TDRP	ENST00000523656.5	c.124T>G	p.Phe42Val	missense_variant	3/5	5		ENSP00000430325.1
TDRP	ENST00000524229.1	n.55T>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Apr 22, 2022

The c.124T>G (p.F42V) alteration is located in exon 2 (coding exon 2) of the TDRP gene. This alteration results from a T to G substitution at nucleotide position 124, causing the phenylalanine (F) at amino acid position 42 to be replaced by a valine (V). 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	0.38
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T;T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.82	T;T;.;.
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.3	M;M;M;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.3	D;.;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0070	D;.;D;D
Sift4G	Uncertain	0.025	D;D;D;D
Polyphen		0.95	.;P;P;.
Vest4		0.83
MutPred		0.22		Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);
MVP		0.31
MPC		0.0059
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.14

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-444582;