16-21404768-C-G

Variant names:

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

Variant summary

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

The NM_130464.3(NPIPB3):​c.1168G>C​(p.Glu390Gln) 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. 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. E390K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 6)
  • Exomes 𝑓: 0.0000051 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB3 NM_130464.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.12510744).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130464.3. 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>C	p.Glu390Gln	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>C	p.Glu174Gln	missense	Exon 1 of 2	ENSP00000444096.1	Q92617-4
	ENSG00000290192	ENST00000703536.1		n.239+3574C>G		intron	N/A
	ENSG00000290192	ENST00000790072.1		n.98+2057C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD2 exomes AF: 0.0000367 AC: 2 AN: 54560 AF XY: 0.0000365

Gnomad AFR exome AF: 0.000191

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000129

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000514 AC: 6 AN: 1168404 Hom.: 0 Cov.: 18 AF XY: 0.00000337 AC XY: 2 AN XY: 593468

⚠️ 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: 26590

American (AMR) AF: 0.00 AC: 0 AN: 41818

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

East Asian (EAS) AF: 0.0000278 AC: 1 AN: 35908

South Asian (SAS) AF: 0.00 AC: 0 AN: 77000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37908

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

European-Non Finnish (NFE) AF: 0.00000459 AC: 4 AN: 871032

Other (OTH) AF: 0.00 AC: 0 AN: 50468

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00578695), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 6

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.4
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.029
Sift	Benign	0.083	T
Sift4G	Benign	0.35	T
Vest4		0.086
MVP		0.043
ClinPred		0.078	T
gMVP		0.0066

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;