16-22533974-C-T

Variant names:

• chr16-22533974-C-T
• rs1282504326
• NM_001395849.1:c.991C>T

Variant summary

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

The NM_001395849.1(NPIPB5):​c.991C>T​(p.Leu331Phe) 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. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000092 (0 hom., cov: 13)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908

Genes affected

NPIPB5 (HGNC:37233): (nuclear pore complex interacting protein family member B5) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC105371131 (HGNC:):

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=0.16358685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB5	NM_001395849.1	c.991C>T	p.Leu331Phe	missense_variant	Exon 7 of 7	ENST00000424340.7	NP_001382778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7	c.991C>T	p.Leu331Phe	missense_variant	Exon 7 of 7	1	NM_001395849.1	ENSP00000440703.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 108322 Hom.: 0 Cov.: 13 FAILED QC

Gnomad AFR AF: 0.0000310

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 Cov.: 27

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000923 AC: 1 AN: 108322 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 52494

Gnomad4 AFR AF: 0.0000310

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.097	.;.;T;T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.83	.;T;T;.;D;.
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-2.3	N;.;N;N;N;.
REVEL	Benign	0.037
Sift	Uncertain	0.0070	D;.;D;D;D;.
Sift4G	Benign	0.63	T;T;T;T;T;T
Polyphen		1.0	.;.;D;D;.;.
Vest4		0.16, 0.11, 0.17, 0.14
MutPred		0.32		Loss of phosphorylation at S334 (P = 0.1599);Loss of phosphorylation at S334 (P = 0.1599);Loss of phosphorylation at S334 (P = 0.1599);Loss of phosphorylation at S334 (P = 0.1599);Loss of phosphorylation at S334 (P = 0.1599);.;
MVP		0.055
ClinPred		0.53	D
Varity_R		0.19
gMVP		0.0035

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: rs1282504326; hg19: chr16-22545295;