chr2-216859687-T-G

Variant names:

• chr2-216859687-T-G
• rs760854000
• NM_003284.4:c.148A>C

Variant summary

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

The NM_003284.4(TNP1):​c.148A>C​(p.Asn50His) 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. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. N50D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNP1 NM_003284.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 0 publications found

Genes affected

TNP1 (HGNC:11951): (transition protein 1) Transition protein-1 is a spermatid-specific product of the haploid genome which replaces histone and is itself replaced in the mature sperm by the protamines (see PRM1, MIM 182880; PRM2, MIM 182890) (Luerssen et al., 1990 [PubMed 2249851]).[supplied by OMIM, Mar 2008]

TESHL (HGNC:52740): (testicular germ cell expressed HSF2 interacting lncRNA)

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=0.25177926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNP1	NM_003284.4	c.148A>C	p.Asn50His	missense_variant	Exon 2 of 2	ENST00000236979.2	NP_003275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNP1	ENST00000236979.2	c.148A>C	p.Asn50His	missense_variant	Exon 2 of 2	1	NM_003284.4	ENSP00000236979.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251214 AF XY: 0.00000737

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.089
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.98	T
PhyloP100		2.1
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.082
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0030	B
Vest4		0.16
MutPred		0.41		Loss of stability (P = 0.0472);
MVP		0.17
MPC		0.19
ClinPred		0.51	D
GERP RS		4.1
PromoterAI		-0.0058	Neutral
Varity_R		0.33
gMVP		0.077
Mutation Taster		=92/8	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: rs760854000; hg19: chr2-217724410;