16-21405020-C-T

Variant names:

• chr16-21405020-C-T
• rs1434714251
• ENST00000542817.1:c.268G>A

Variant summary

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

The NM_130464.3(NPIPB3):​c.916G>A​(p.Glu306Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/16 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. E306Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 5)
  • Exomes 𝑓: 0.000044 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB3 NM_130464.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 1 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=0.151501).

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.916G>A	p.Glu306Lys	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.268G>A	p.Glu90Lys	missense	Exon 1 of 2	ENSP00000444096.1	Q92617-4
	NPIPB3	ENST00000504841.6	TSL:1	c.916G>A	p.Glu306Lys	missense	Exon 7 of 7	ENSP00000446048.1	F5H4N5
	ENSG00000290192	ENST00000703536.1		n.239+3826C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD2 exomes AF: 0.0000912 AC: 5 AN: 54808 AF XY: 0.000110

Gnomad AFR exome AF: 0.00

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: 0.000142

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000440 AC: 30 AN: 682022 Hom.: 0 Cov.: 10 AF XY: 0.0000467 AC XY: 17 AN XY: 364046

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

African (AFR) AF: 0.00 AC: 0 AN: 18064

American (AMR) AF: 0.00 AC: 0 AN: 36368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20650

East Asian (EAS) AF: 0.00 AC: 0 AN: 33412

South Asian (SAS) AF: 0.000152 AC: 10 AN: 65582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2618

European-Non Finnish (NFE) AF: 0.0000438 AC: 19 AN: 434282

Other (OTH) AF: 0.0000290 AC: 1 AN: 34502

⚠️ 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 Cov.: 5

Alfa AF: 0.000149 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.0
DANN	Uncertain	0.98
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.3
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.019
Sift	Benign	0.097	T
Sift4G	Benign	0.36	T
Vest4		0.17
MVP		0.043
ClinPred		0.16	T
PromoterAI		0.0062	Neutral
gMVP		0.025
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: rs1434714251; hg19: chr16-21416341;