Variant chr16-11268872-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005425.5(TNP2):c.391C>T(p.Arg131Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,577,960 control chromosomes in the GnomAD database, including 209,983 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.44 ( 15797 hom., cov: 31)

Exomes 𝑓: 0.51 ( 194186 hom. )

Consequence

TNP2
NM_005425.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13

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]

TNP2 links:

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]

RMI2 links:

RMI2 (HGNC:):

RMI2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4927983E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNP2	NM_005425.5 linkuse as main transcript	c.391C>T	p.Arg131Trp	missense_variant	1/2	ENST00000312693.4	NP_005416.1	Q05952Q4VB56
LOC105371082	XR_933070.4 linkuse as main transcript	n.178+19094G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNP2	ENST00000312693.4 linkuse as main transcript	c.391C>T	p.Arg131Trp	missense_variant	1/2	1	NM_005425.5	ENSP00000325738.3		Q05952

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66332

AN:

151758

Hom.:

15802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.621

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.463

GnomAD3 exomes

AF:

0.437

AC:

97017

AN:

221988

Hom.:

23295

AF XY:

0.444

AC XY:

53288

AN XY:

120072

show subpopulations

Gnomad AFR exome

AF:

0.276

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.410

Gnomad EAS exome

AF:

0.247

Gnomad SAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.582

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.512

AC:

730077

AN:

1426084

Hom.:

194186

Cov.:

AF XY:

0.507

AC XY:

358308

AN XY:

706452

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.280

Gnomad4 ASJ exome

AF:

0.413

Gnomad4 EAS exome

AF:

0.229

Gnomad4 SAS exome

AF:

0.326

Gnomad4 FIN exome

AF:

0.585

Gnomad4 NFE exome

AF:

0.552

Gnomad4 OTH exome

AF:

0.489

GnomAD4 genome

AF:

0.437

AC:

66311

AN:

151876

Hom.:

15797

Cov.:

AF XY:

0.433

AC XY:

32161

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.283

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.412

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.316

Gnomad4 FIN

AF:

0.582

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.459

Alfa

AF:

0.506

Hom.:

46687

Bravo

AF:

0.412

TwinsUK

AF:

0.550

AC:

2041

ALSPAC

AF:

0.535

AC:

2060

ESP6500AA

AF:

0.272

AC:

1080

ESP6500EA

AF:

0.534

AC:

4437

ExAC

AF:

0.436

AC:

52744

Asia WGS

AF:

0.282

AC:

981

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.71

T;T

MetaRNN

Benign

0.00015

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.5

.;L

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-5.5

.;D

REVEL

Benign

0.068

Sift

Benign

0.078

.;T

Sift4G

Uncertain

0.0020

.;D

Polyphen

0.89

.;P

Vest4

0.31

MPC

0.38

ClinPred

0.064

GERP RS

1.7

Varity_R

0.11

gMVP

0.0027

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over