ENST00000542817.1:c.520G>A

Variant names:

• chr16-21404768-C-T
• rs1360962621
• ENST00000542817.1:c.520G>A

Variant summary

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

The ENST00000542817.1(NPIPB3):​c.520G>A​(p.Glu174Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 6)
  • Exomes 𝑓: 0.00029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB3 ENST00000542817.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.42
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09147507).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000542817.1. 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
	NPIPB3	NM_130464.3		c.1168G>A	p.Glu390Lys	missense	Exon 8 of 12	NP_569731.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB3	ENST00000542817.1	TSL:5	c.520G>A	p.Glu174Lys	missense	Exon 1 of 2	ENSP00000444096.1	Q92617-4
	ENSG00000290192	ENST00000703536.1		n.239+3574C>T		intron	N/A
	ENSG00000290192	ENST00000790072.1		n.98+2057C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 4 AN: 33940 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.000146

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: 0.000159

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000147 AC: 8 AN: 54560 AF XY: 0.000110

Gnomad AFR exome AF: 0.000191

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000339

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000285 AC: 333 AN: 1168282 Hom.: 0 Cov.: 18 AF XY: 0.000285 AC XY: 169 AN XY: 593404

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000376 AC: 1 AN: 26592

American (AMR) AF: 0.0000478 AC: 2 AN: 41818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24108

East Asian (EAS) AF: 0.00 AC: 0 AN: 35908

South Asian (SAS) AF: 0.0000390 AC: 3 AN: 76998

European-Finnish (FIN) AF: 0.0000264 AC: 1 AN: 37906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3572

European-Non Finnish (NFE) AF: 0.000365 AC: 318 AN: 870922

Other (OTH) AF: 0.000159 AC: 8 AN: 50458

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000118 AC: 4 AN: 33940 Hom.: 0 Cov.: 6 AF XY: 0.000175 AC XY: 3 AN XY: 17166

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000146 AC: 1 AN: 6834

American (AMR) AF: 0.00 AC: 0 AN: 3266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 968

East Asian (EAS) AF: 0.00 AC: 0 AN: 684

South Asian (SAS) AF: 0.00 AC: 0 AN: 342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 24

European-Non Finnish (NFE) AF: 0.000159 AC: 3 AN: 18824

Other (OTH) AF: 0.00 AC: 0 AN: 458

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000401256), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000743 Hom.: 0

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
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.6
DANN	Uncertain	1.0
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.4
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.011
Sift	Benign	0.28	T
Sift4G	Benign	0.65	T
Vest4		0.12
MVP		0.043
ClinPred		0.064	T
gMVP		0.010
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1360962621; hg19: chr16-21416089; COSMIC: COSV101341656; COSMIC: COSV101341656;