chr8-492743-T-C

Position:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001384899.1(TDRP):ā€‹c.214A>Gā€‹(p.Thr72Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,448,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000035 ( 0 hom. )

Consequence

TDRP
NM_001384899.1 missense, splice_region

Scores

3
16
Splicing: ADA: 0.0001185
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.301
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06257695).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TDRPNM_001384899.1 linkuse as main transcriptc.214A>G p.Thr72Ala missense_variant, splice_region_variant 3/3 ENST00000324079.11 NP_001371828.1
TDRPNM_001256113.2 linkuse as main transcriptc.214A>G p.Thr72Ala missense_variant, splice_region_variant 3/4 NP_001243042.1 Q86YL5-2
TDRPNM_175075.5 linkuse as main transcriptc.214A>G p.Thr72Ala missense_variant, splice_region_variant 4/4 NP_778250.2 Q86YL5-1
TDRPXM_047421392.1 linkuse as main transcriptc.244A>G p.Thr82Ala missense_variant, splice_region_variant 4/4 XP_047277348.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TDRPENST00000324079.11 linkuse as main transcriptc.214A>G p.Thr72Ala missense_variant, splice_region_variant 3/31 NM_001384899.1 ENSP00000315111.6 Q86YL5-1
TDRPENST00000523656.5 linkuse as main transcriptc.214A>G p.Thr72Ala missense_variant, splice_region_variant 4/55 ENSP00000430325.1 Q86YL5-2
TDRPENST00000524229.1 linkuse as main transcriptn.145A>G splice_region_variant, non_coding_transcript_exon_variant 3/33

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000417
AC:
1
AN:
239676
Hom.:
0
AF XY:
0.00000768
AC XY:
1
AN XY:
130222
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000301
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000345
AC:
5
AN:
1448036
Hom.:
0
Cov.:
32
AF XY:
0.00000556
AC XY:
4
AN XY:
718982
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000231
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:
0.00000272
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
ExAC
AF:
0.00000828
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 02, 2021The c.214A>G (p.T72A) 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 214, causing the threonine (T) at amino acid position 72 to be replaced by an alanine (A). 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
0.082
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
7.4
DANN
Benign
0.90
DEOGEN2
Benign
0.11
.;T;T;.
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.61
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.60
T;T;.;.
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.063
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.0
M;M;M;M
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-2.9
D;.;N;D
REVEL
Benign
0.094
Sift
Benign
0.074
T;.;T;T
Sift4G
Benign
0.10
T;T;T;T
Polyphen
0.0080
.;B;B;.
Vest4
0.25
MutPred
0.049
Loss of phosphorylation at T72 (P = 0.0277);Loss of phosphorylation at T72 (P = 0.0277);Loss of phosphorylation at T72 (P = 0.0277);Loss of phosphorylation at T72 (P = 0.0277);
MVP
0.030
MPC
0.0030
ClinPred
0.089
T
GERP RS
0.58
Varity_R
0.048
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00012
dbscSNV1_RF
Benign
0.016
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769226461; hg19: chr8-442743; API