13-44959414-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_012345.3(NUFIP1):​c.988G>C​(p.Asp330His) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NUFIP1
NM_012345.3 missense

Scores

2
15
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97
Variant links:
Genes affected
NUFIP1 (HGNC:8057): (nuclear FMR1 interacting protein 1) This gene encodes a nuclear RNA binding protein that contains a C2H2 zinc finger motif and a nuclear localization signal. This protein is associated with the nuclear matrix in perichromatin fibrils and, in neurons, localizes to the cytoplasm in association with endoplasmic reticulum ribosomes. This protein interacts with the fragile X mental retardation protein (FMRP), the tumor suppressor protein BRCA1, upregulates RNA polymerase II transcription, and is involved in box C/D snoRNP biogenesis. A pseudogene of this gene resides on chromosome 6q12. [provided by RefSeq, Feb 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.768

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NUFIP1NM_012345.3 linkc.988G>C p.Asp330His missense_variant Exon 7 of 10 ENST00000379161.5 NP_036477.2 Q9UHK0
NUFIP1XR_941559.3 linkn.1023G>C non_coding_transcript_exon_variant Exon 7 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NUFIP1ENST00000379161.5 linkc.988G>C p.Asp330His missense_variant Exon 7 of 10 1 NM_012345.3 ENSP00000368459.4 Q9UHK0

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461588
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
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:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.988G>C (p.D330H) alteration is located in exon 7 (coding exon 7) of the NUFIP1 gene. This alteration results from a G to C substitution at nucleotide position 988, causing the aspartic acid (D) at amino acid position 330 to be replaced by a histidine (H). 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
0.68
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.50
T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.81
T
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.77
D
MetaSVM
Uncertain
0.091
D
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-4.2
D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0050
D
Polyphen
1.0
D
Vest4
0.58
MutPred
0.32
Gain of catalytic residue at L332 (P = 0.0012);
MVP
0.95
MPC
0.35
ClinPred
0.99
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.38
gMVP
0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1160678113; hg19: chr13-45533549; API