rs11640138

chr16-11268872-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 12/19 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

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]

LOC105371082 (HGNC:):

ACMG classification

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	UniProt
TNP2	NM_005425.5	c.391C>T	p.Arg131Trp	missense_variant	1/2	ENST00000312693.4
LOC105371082	XR_933070.4	n.178+19094G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNP2	ENST00000312693.4	c.391C>T	p.Arg131Trp	missense_variant	1/2	1	NM_005425.5	P1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66332 AN: 151758 Hom.: 15802 Cov.: 31

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

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.: 57 AF XY: 0.507 AC XY: 358308 AN XY: 706452

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.: 31 AF XY: 0.433 AC XY: 32161 AN XY: 74226

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	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	20
Dann	Uncertain	1.0
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.71	T;T
MetaRNN	Benign	0.00015	T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.24	T
Polyphen		0.89	.;P
Vest4		0.31
MPC		0.38
ClinPred		0.064	T
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

Other links and lift over

dbSNP: rs11640138; hg19: chr16-11362729; COSMIC: COSV57129629; COSMIC: COSV57129629;