16-22533837-C-A

Variant names:

• chr16-22533837-C-A
• rs2049883168
• NM_001395849.1:c.854C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001395849.1(NPIPB5):​c.854C>A​(p.Pro285His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P285L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 4)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28842857).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395849.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB5	NM_001395849.1	MANE Select	c.854C>A	p.Pro285His	missense	Exon 7 of 7	NP_001382778.1	A8MRT5
	NPIPB5	NM_001135865.3		c.854C>A	p.Pro285His	missense	Exon 9 of 9	NP_001129337.1	A8MRT5
	NPIPB5	NM_001395850.1		c.854C>A	p.Pro285His	missense	Exon 8 of 8	NP_001382779.1	A8MRT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB5	ENST00000424340.7	TSL:1 MANE Select	c.854C>A	p.Pro285His	missense	Exon 7 of 7	ENSP00000440703.1	A8MRT5
	NPIPB5	ENST00000528249.5	TSL:1	c.854C>A	p.Pro285His	missense	Exon 7 of 7	ENSP00000431553.1	E9PKP1
	NPIPB5	ENST00000517539.6	TSL:5	c.854C>A	p.Pro285His	missense	Exon 8 of 8	ENSP00000430633.1	A8MRT5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 11542 Hom.: 0 Cov.: 4

Gnomad AFR AF: 0.00

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.: 0

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 11542 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 5812

African (AFR) AF: 0.00 AC: 0 AN: 4490

American (AMR) AF: 0.00 AC: 0 AN: 1276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 286

East Asian (EAS) AF: 0.00 AC: 0 AN: 254

South Asian (SAS) AF: 0.00 AC: 0 AN: 154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 20

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4350

Other (OTH) AF: 0.00 AC: 0 AN: 86

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.90
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.094
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.079
MutPred		0.52		Loss of glycosylation at P285 (P = 0.0639)
MVP		0.25
ClinPred		0.96	D
Varity_R		0.21
gMVP		0.036
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs2049883168; hg19: chr16-22545158;