14-24408145-G-C

Variant names:

• chr14-24408145-G-C
• NM_025081.3:c.475G>C
• NYNRIN p.Val159Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025081.3(NYNRIN):​c.475G>C​(p.Val159Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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 the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NYNRIN NM_025081.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25
• Publications: 0 publications found

Genes affected

NYNRIN (HGNC:20165): (NYN domain and retroviral integrase containing) Predicted to enable endoribonuclease activity and mRNA binding activity. Predicted to be involved in RNA phosphodiester bond hydrolysis, endonucleolytic. Predicted to be integral component of membrane. Predicted to be active in cytoplasmic ribonucleoprotein granule and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31181446).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025081.3. 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
	NYNRIN	NM_025081.3	MANE Select	c.475G>C	p.Val159Leu	missense	Exon 3 of 9	NP_079357.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NYNRIN	ENST00000382554.4	TSL:5 MANE Select	c.475G>C	p.Val159Leu	missense	Exon 3 of 9	ENSP00000371994.3	Q9P2P1-1
	NYNRIN	ENST00000938047.1		c.475G>C	p.Val159Leu	missense	Exon 2 of 8	ENSP00000608106.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.19
gMVP		0.55
Mutation Taster		=94/6	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-24877351;