rs1400905049

Variant names:

• chr16-22534010-C-T
• rs1400905049
• NM_001395849.1:c.1027C>T

Variant summary

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

The NM_001395849.1(NPIPB5):​c.1027C>T​(p.Pro343Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 15)
  • Exomes 𝑓: 0.000030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.904
• Publications: 0 publications found

Genes affected

NPIPB5 (HGNC:37233): (nuclear pore complex interacting protein family member B5) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC105371131 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026281863).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395849.1. 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
	NPIPB5	NM_001395849.1	MANE Select	c.1027C>T	p.Pro343Ser	missense	Exon 7 of 7	NP_001382778.1	A8MRT5
	NPIPB5	NM_001135865.3		c.1027C>T	p.Pro343Ser	missense	Exon 9 of 9	NP_001129337.1	A8MRT5
	NPIPB5	NM_001395850.1		c.1027C>T	p.Pro343Ser	missense	Exon 8 of 8	NP_001382779.1	A8MRT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPB5	ENST00000424340.7	TSL:1 MANE Select	c.1027C>T	p.Pro343Ser	missense	Exon 7 of 7	ENSP00000440703.1	A8MRT5
	NPIPB5	ENST00000528249.5	TSL:1	c.1027C>T	p.Pro343Ser	missense	Exon 7 of 7	ENSP00000431553.1	E9PKP1
	NPIPB5	ENST00000517539.6	TSL:5	c.1027C>T	p.Pro343Ser	missense	Exon 8 of 8	ENSP00000430633.1	A8MRT5

Frequencies

GnomAD3 genomes AF: 0.000314 AC: 38 AN: 121104 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.00105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000845

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: 0.000163 AC: 10 AN: 61504 AF XY: 0.000132

Gnomad AFR exome AF: 0.00153

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000126

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: 0.0000302 AC: 43 AN: 1421496 Hom.: 0 Cov.: 32 AF XY: 0.0000240 AC XY: 17 AN XY: 708428

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

African (AFR) AF: 0.00102 AC: 34 AN: 33200

American (AMR) AF: 0.000113 AC: 5 AN: 44178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41050

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4098

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088434

Other (OTH) AF: 0.0000337 AC: 2 AN: 59348

⚠️ 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: 0.000314 AC: 38 AN: 121104 Hom.: 0 Cov.: 15 AF XY: 0.000273 AC XY: 16 AN XY: 58680

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

African (AFR) AF: 0.00105 AC: 37 AN: 35398

American (AMR) AF: 0.0000845 AC: 1 AN: 11828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2976

East Asian (EAS) AF: 0.00 AC: 0 AN: 3432

South Asian (SAS) AF: 0.00 AC: 0 AN: 3546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53528

Other (OTH) AF: 0.00 AC: 0 AN: 1664

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000253 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	0.21
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.3
DANN	Benign	0.48
DEOGEN2	Benign	0.099	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.90
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.027
Sift	Benign	0.20	T
Sift4G	Uncertain	0.022	D
Polyphen		0.018	B
Vest4		0.065
MutPred		0.47		Loss of catalytic residue at P342 (P = 0.016)
MVP		0.030
ClinPred		0.028	T
Varity_R		0.073
gMVP		0.0049

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1400905049; hg19: chr16-22545331;