17-29286762-G-T

Position:

• chr17-29286762-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000225388.9(NUFIP2):​c.1232C>A​(p.Ser411Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUFIP2 ENST00000225388.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUFIP2	NM_020772.3	c.1232C>A	p.Ser411Tyr	missense_variant	2/4	ENST00000225388.9	NP_065823.1
NUFIP2	XM_017024896.3	c.755C>A	p.Ser252Tyr	missense_variant	2/4		XP_016880385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUFIP2	ENST00000225388.9	c.1232C>A	p.Ser411Tyr	missense_variant	2/4	1	NM_020772.3	ENSP00000225388	P1
NUFIP2	ENST00000579665.1	c.277+7021C>A		intron_variant		1		ENSP00000463450

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

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

May 28, 2024

The c.1232C>A (p.S411Y) 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 1232, causing the serine (S) at amino acid position 411 to be replaced by a tyrosine (Y). 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	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.98	D
Vest4		0.96
MutPred		0.44		Gain of sheet (P = 0.0101);
MVP		0.36
MPC		0.61
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.75
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-27613780;