Variant 17-29286658-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000225388.9(NUFIP2):c.1336A>C(p.Ile446Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I446V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NUFIP2
ENST00000225388.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101

Variant links:

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]

NUFIP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04284823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUFIP2	NM_020772.3 linkuse as main transcript	c.1336A>C	p.Ile446Leu	missense_variant	2/4	ENST00000225388.9	NP_065823.1
NUFIP2	XM_017024896.3 linkuse as main transcript	c.859A>C	p.Ile287Leu	missense_variant	2/4		XP_016880385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUFIP2	ENST00000225388.9 linkuse as main transcript	c.1336A>C	p.Ile446Leu	missense_variant	2/4	1	NM_020772.3	ENSP00000225388	P1	Q7Z417-1
NUFIP2	ENST00000579665.1 linkuse as main transcript	c.277+7125A>C		intron_variant		1		ENSP00000463450		Q7Z417-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.1336A>C (p.I446L) alteration is located in exon 2 (coding exon 2) of the NUFIP2 gene. This alteration results from a A to C substitution at nucleotide position 1336, causing the isoleucine (I) at amino acid position 446 to be replaced by a leucine (L). 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

0.073

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.011

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.92

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.67

M_CAP

Benign

0.0063

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.54

REVEL

Benign

0.079

Sift

Benign

0.61

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.22

MutPred

0.15

Gain of disorder (P = 0.0542);

MVP

0.068

MPC

0.11

ClinPred

0.021

GERP RS

-0.036

Varity_R

0.059

gMVP

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over