chr16-21424993-C-T

Variant names:

• chr16-21424993-C-T
• rs1555474623
• ENST00000504841.6:c.106G>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.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. 12/16 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
• 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=0.109314024).

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.106G>A	p.Glu36Lys	missense	Exon 2 of 12	NP_569731.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB3	ENST00000504841.6	TSL:1	c.106G>A	p.Glu36Lys	missense	Exon 1 of 7	ENSP00000446048.1	F5H4N5
	NPIPB3	ENST00000419180.6	TSL:3	c.11G>A	p.Arg4Gln	missense	Exon 2 of 9	ENSP00000413141.2	C9K082
	NPIPB3	ENST00000534903.1	TSL:4	c.106G>A	p.Glu36Lys	missense	Exon 3 of 5	ENSP00000439062.1	F5H3W2

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

African (AFR) AF: 0.00 AC: 0 AN: 10390

American (AMR) AF: 0.00 AC: 0 AN: 10040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3802

East Asian (EAS) AF: 0.00 AC: 0 AN: 13786

South Asian (SAS) AF: 0.00 AC: 0 AN: 27618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 70384

Other (OTH) AF: 0.00 AC: 0 AN: 8602

GnomAD4 genome Cov.: 3

Alfa AF: 0.00 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	0.30
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
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.023
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.096
Sift	Benign	0.27	T
Sift4G	Benign	0.40	T
MutPred		0.50		Gain of methylation at E36 (P = 0)
MVP		0.29
ClinPred		0.068	T
GERP RS		-0.46
PromoterAI		-0.012	Neutral

Splicing

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

Other links and lift over

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