16-11268961-C-A

Variant names:

• chr16-11268961-C-A
• rs759134912
• NM_005425.5:c.302G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005425.5(TNP2):​c.302G>T​(p.Arg101Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,612 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TNP2 NM_005425.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10977328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005425.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNP2	NM_005425.5	MANE Select	c.302G>T	p.Arg101Leu	missense	Exon 1 of 2	NP_005416.1	Q05952

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNP2	ENST00000312693.4	TSL:1 MANE Select	c.302G>T	p.Arg101Leu	missense	Exon 1 of 2	ENSP00000325738.3	Q05952
	RMI2	ENST00000572173.1	TSL:1	c.-516+19183C>A		intron	N/A	ENSP00000461206.1	Q96E14-2
	TNP2	ENST00000560751.1	TSL:6	c.302G>T	p.Arg101Leu	missense	Exon 1 of 1	ENSP00000496261.1	A0A2R8Y7P0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461612 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727098

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111840

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.0070
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.074
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.011	D
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.41		Loss of MoRF binding (P = 0.0098)
MVP		0.32
MPC		0.088
ClinPred		0.29	T
GERP RS		2.6
PromoterAI		-0.030	Neutral
Varity_R		0.11
gMVP		0.025
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs759134912; hg19: chr16-11362818;