rs17066364

Positions:

• chr13-44941854-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012345.3(NUFIP1):​c.1372-532C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 152,118 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.032 (106 hom., cov: 32)
• Consequence: NUFIP1 NM_012345.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUFIP1	NM_012345.3	c.1372-532C>G		intron_variant		ENST00000379161.5	NP_036477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUFIP1	ENST00000379161.5	c.1372-532C>G		intron_variant		1	NM_012345.3	ENSP00000368459.4

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4860 AN: 151998 Hom.: 107 Cov.: 32

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0479

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0713

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0319 AC: 4854 AN: 152118 Hom.: 106 Cov.: 32 AF XY: 0.0337 AC XY: 2505 AN XY: 74362

Gnomad4 AFR AF: 0.0292

Gnomad4 AMR AF: 0.0478

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0703

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0239

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0300 Hom.: 19

Bravo AF: 0.0328

Asia WGS AF: 0.104 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs17066364; hg19: chr13-45515989;