16-21402885-G-A

Variant names:

• chr16-21402885-G-A
• ENST00000542817.1:c.662C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_130464.3(NPIPB3):​c.2795C>T​(p.Pro932Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: NPIPB3 NM_130464.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.161

Genes affected

NPIPB3 (HGNC:28989): (nuclear pore complex interacting protein family member B3) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000290192 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15660879).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB3	NM_130464.3	c.2795C>T	p.Pro932Leu	missense_variant	Exon 12 of 12		NP_569731.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB3	ENST00000542817.1	c.662C>T	p.Pro221Leu	missense_variant	Exon 2 of 2	5		ENSP00000444096.1
ENSG00000290192	ENST00000703536.1	n.239+1691G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2801C>T (p.P934L) alteration is located in exon 9 (coding exon 8) of the NPIPB3 gene. This alteration results from a C to T substitution at nucleotide position 2801, causing the proline (P) at amino acid position 934 to be replaced by a leucine (L). 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
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.00088	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.94	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.046
Sift	Benign	0.11	T
Sift4G	Uncertain	0.0030	D
Vest4		0.14
MVP		0.043
ClinPred		0.64	D
gMVP		0.0079

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-21414206;