17-29286151-G-T

Position:

• chr17-29286151-G-T

Variant summary

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

The NM_020772.3(NUFIP2):​c.1843C>A​(p.Leu615Ile) 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. 12/20 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: NUFIP2 NM_020772.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

Genes affected

NUFIP2 (HGNC:17634): (nuclear FMR1 interacting protein 2) Enables RNA binding activity. Located in cytoplasmic stress granule; cytosol; and nuclear body. Part of polysomal ribosome. [provided by Alliance of Genome Resources, Apr 2022]

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=0.24593276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUFIP2	NM_020772.3	c.1843C>A	p.Leu615Ile	missense_variant	2/4	ENST00000225388.9	NP_065823.1
NUFIP2	XM_017024896.3	c.1366C>A	p.Leu456Ile	missense_variant	2/4		XP_016880385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUFIP2	ENST00000225388.9	c.1843C>A	p.Leu615Ile	missense_variant	2/4	1	NM_020772.3	ENSP00000225388	P1
NUFIP2	ENST00000579665.1	c.277+7632C>A		intron_variant		1		ENSP00000463450

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 29, 2022

The c.1843C>A (p.L615I) alteration is located in exon 2 (coding exon 2) of the NUFIP2 gene. This alteration results from a C to A substitution at nucleotide position 1843, causing the leucine (L) at amino acid position 615 to be replaced by an isoleucine (I). 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	0.12
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.094
Sift	Benign	0.34	T
Sift4G	Benign	0.29	T
Polyphen		0.94	P
Vest4		0.42
MutPred		0.28		Gain of sheet (P = 0.0221);
MVP		0.28
MPC		0.18
ClinPred		0.52	D
GERP RS		5.0
Varity_R		0.17
gMVP		0.086

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: chr17-27613169;