NM_005425.5:c.302G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005425.5(TNP2):​c.302G>C​(p.Arg101Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R101H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TNP2
NM_005425.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00700
Variant links:
Genes affected
TNP2 (HGNC:11952): (transition protein 2) Predicted to enable zinc ion binding activity. Predicted to be involved in positive regulation of protein processing; single fertilization; and spermatogenesis, exchange of chromosomal proteins. Predicted to act upstream of or within binding activity of sperm to zona pellucida and flagellated sperm motility. Predicted to be located in nucleus. Predicted to be part of nucleosome. [provided by Alliance of Genome Resources, Apr 2022]
RMI2 (HGNC:28349): (RecQ mediated genome instability 2) RMI2 is a component of the BLM (RECQL3; MIM 604610) complex, which plays a role in homologous recombination-dependent DNA repair and is essential for genome stability (Xu et al., 2008 [PubMed 18923082]).[supplied by OMIM, Nov 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07276189).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNP2NM_005425.5 linkc.302G>C p.Arg101Pro missense_variant Exon 1 of 2 ENST00000312693.4 NP_005416.1 Q05952Q4VB56
LOC105371082XR_933070.4 linkn.178+19183C>G intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNP2ENST00000312693.4 linkc.302G>C p.Arg101Pro missense_variant Exon 1 of 2 1 NM_005425.5 ENSP00000325738.3 Q05952

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152108
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000918
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249250
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135214
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000870
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:
0.00000684
AC:
10
AN:
1461612
Hom.:
0
Cov.:
33
AF XY:
0.00000550
AC XY:
4
AN XY:
727098
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
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:
0.00
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152108
Hom.:
0
Cov.:
32
AF XY:
0.000135
AC XY:
10
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000918
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000957
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.000121
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.302G>C (p.R101P) alteration is located in exon 1 (coding exon 1) of the TNP2 gene. This alteration results from a G to C substitution at nucleotide position 302, causing the arginine (R) at amino acid position 101 to be replaced by a proline (P). 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
0.11
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
15
DANN
Benign
0.87
DEOGEN2
Benign
0.055
.;T
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.39
T;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.073
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
.;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.22
.;N
REVEL
Benign
0.066
Sift
Uncertain
0.010
.;D
Sift4G
Uncertain
0.019
.;D
Polyphen
0.0020
.;B
Vest4
0.21
MutPred
0.42
Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);
MVP
0.30
MPC
0.10
ClinPred
0.12
T
GERP RS
2.6
Varity_R
0.17
gMVP
0.016

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

LitVar

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

Other links and lift over

dbSNP: rs759134912; hg19: chr16-11362818; API