NM_005425.5:c.12G>C

Variant names:

• chr16-11269251-C-G
• NM_005425.5:c.12G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005425.5(TNP2):​c.12G>C​(p.Gln4His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNP2 NM_005425.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

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 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=0.12235239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNP2	NM_005425.5	c.12G>C	p.Gln4His	missense_variant	Exon 1 of 2	ENST00000312693.4	NP_005416.1
LOC105371082	XR_933070.4	n.178+19473C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNP2	ENST00000312693.4	c.12G>C	p.Gln4His	missense_variant	Exon 1 of 2	1	NM_005425.5	ENSP00000325738.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.12G>C (p.Q4H) 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 12, causing the glutamine (Q) at amino acid position 4 to be replaced by a histidine (H). 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	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.9	.;N
REVEL	Benign	0.034
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.0060	.;D
Polyphen		0.019	.;B
Vest4		0.18
MutPred		0.33		Gain of glycosylation at T3 (P = 0.0958);Gain of glycosylation at T3 (P = 0.0958);
MVP		0.33
MPC		0.068
ClinPred		0.28	T
GERP RS		2.6
Varity_R		0.19
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-11363108;