16-21424993-C-T

Variant names:

• chr16-21424993-C-T
• rs1555474623
• ENST00000504841.6:c.106G>A

Variant summary

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

The NM_130464.3(NPIPB3):​c.106G>A​(p.Glu36Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 3)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB3 NM_130464.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0230

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=0.109314024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB3	NM_130464.3	c.106G>A	p.Glu36Lys	missense_variant	Exon 2 of 12		NP_569731.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB3	ENST00000504841.6	c.106G>A	p.Glu36Lys	missense_variant	Exon 1 of 7	1		ENSP00000446048.1
NPIPB3	ENST00000419180.6	c.11G>A	p.Arg4Gln	missense_variant	Exon 2 of 9	3		ENSP00000413141.2
NPIPB3	ENST00000534903.1	c.106G>A	p.Glu36Lys	missense_variant	Exon 3 of 5	4		ENSP00000439062.1

Frequencies

GnomAD3 genomes Cov.: 3

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151960 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81506

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106G>A (p.E36K) alteration is located in exon 2 (coding exon 1) of the NPIPB3 gene. This alteration results from a G to A substitution at nucleotide position 106, causing the glutamic acid (E) at amino acid position 36 to be replaced by a lysine (K). 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	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Uncertain	0.98
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.00062	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.95	T
PROVEAN	Benign	-0.62	N;N
REVEL	Benign	0.096
Sift	Benign	0.27	T;T
Sift4G	Benign	0.40	T;.
MutPred		0.50		Gain of methylation at E36 (P = 0);Gain of methylation at E36 (P = 0);
MVP		0.29
ClinPred		0.068	T
GERP RS		-0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555474623; hg19: chr16-21436314; COSMIC: COSV70019115;