chr16-21405020-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_130464.3(NPIPB3):​c.916G>C​(p.Glu306Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 5)
  • Exomes 𝑓: 0.00030 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB3 NM_130464.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010545284).

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>C	p.Glu306Gln	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>C	p.Glu90Gln	missense	Exon 1 of 2	ENSP00000444096.1	Q92617-4
	NPIPB3	ENST00000504841.6	TSL:1	c.916G>C	p.Glu306Gln	missense	Exon 7 of 7	ENSP00000446048.1	F5H4N5
	ENSG00000290192	ENST00000703536.1		n.239+3826C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000625 AC: 16 AN: 25584 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00345

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00151 AC: 83 AN: 54808 AF XY: 0.000951

Gnomad AFR exome AF: 0.00932

Gnomad AMR exome AF: 0.000563

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000947

Gnomad OTH exome AF: 0.00104

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000298 AC: 203 AN: 681982 Hom.: 2 Cov.: 10 AF XY: 0.000244 AC XY: 89 AN XY: 364052

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

African (AFR) AF: 0.00627 AC: 113 AN: 18012

American (AMR) AF: 0.000302 AC: 11 AN: 36366

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

East Asian (EAS) AF: 0.0000299 AC: 1 AN: 33414

South Asian (SAS) AF: 0.000595 AC: 39 AN: 65592

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2616

European-Non Finnish (NFE) AF: 0.0000322 AC: 14 AN: 434288

Other (OTH) AF: 0.000725 AC: 25 AN: 34500

⚠️ 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: 0.000625 AC: 16 AN: 25594 Hom.: 0 Cov.: 5 AF XY: 0.000376 AC XY: 5 AN XY: 13288

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

African (AFR) AF: 0.00344 AC: 16 AN: 4650

American (AMR) AF: 0.00 AC: 0 AN: 2696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 714

East Asian (EAS) AF: 0.00 AC: 0 AN: 552

South Asian (SAS) AF: 0.00 AC: 0 AN: 232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 18

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14362

Other (OTH) AF: 0.00 AC: 0 AN: 336

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000719773), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000149 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
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.3
DANN	Uncertain	0.99
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.3
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.049
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.28	T
Vest4		0.13
MVP		0.043
ClinPred		0.035	T
PromoterAI		0.016	Neutral
gMVP		0.015
Mutation Taster		=99/1	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;