16-22533744-A-C

Variant names:

• chr16-22533744-A-C
• rs2049882209
• NM_001395849.1:c.761A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395849.1(NPIPB5):​c.761A>C​(p.His254Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 5)
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.37
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19575262).

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.761A>C	p.His254Pro	missense	Exon 7 of 7	NP_001382778.1	A8MRT5
	NPIPB5	NM_001135865.3		c.761A>C	p.His254Pro	missense	Exon 9 of 9	NP_001129337.1	A8MRT5
	NPIPB5	NM_001395850.1		c.761A>C	p.His254Pro	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.761A>C	p.His254Pro	missense	Exon 7 of 7	ENSP00000440703.1	A8MRT5
	NPIPB5	ENST00000528249.5	TSL:1	c.761A>C	p.His254Pro	missense	Exon 7 of 7	ENSP00000431553.1	E9PKP1
	NPIPB5	ENST00000517539.6	TSL:5	c.761A>C	p.His254Pro	missense	Exon 8 of 8	ENSP00000430633.1	A8MRT5

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.6
DANN	Benign	0.51
DEOGEN2	Benign	0.076	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.97	T
PhyloP100		-1.4
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.16
Sift	Uncertain	0.014	D
Sift4G	Benign	0.20	T
Polyphen		0.97	D
Vest4		0.17
MutPred		0.64		Loss of sheet (P = 0.0228)
MVP		0.15
ClinPred		0.40	T
Varity_R		0.40
gMVP		0.0079

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: rs2049882209; hg19: chr16-22545065;