rs1470327269

Variant names:

• chr16-22534050-C-A
• rs1470327269
• NM_001395849.1:c.1067C>A

Variant summary

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

The NM_001395849.1(NPIPB5):​c.1067C>A​(p.Pro356His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 15)
  • Exomes 𝑓: 0.00012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.894
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11440173).

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.1067C>A	p.Pro356His	missense	Exon 7 of 7	NP_001382778.1	A8MRT5
	NPIPB5	NM_001135865.3		c.1067C>A	p.Pro356His	missense	Exon 9 of 9	NP_001129337.1	A8MRT5
	NPIPB5	NM_001395850.1		c.1067C>A	p.Pro356His	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.1067C>A	p.Pro356His	missense	Exon 7 of 7	ENSP00000440703.1	A8MRT5
	NPIPB5	ENST00000528249.5	TSL:1	c.1067C>A	p.Pro356His	missense	Exon 7 of 7	ENSP00000431553.1	E9PKP1
	NPIPB5	ENST00000517539.6	TSL:5	c.1067C>A	p.Pro356His	missense	Exon 8 of 8	ENSP00000430633.1	A8MRT5

Frequencies

GnomAD3 genomes AF: 0.000239 AC: 28 AN: 117190 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.000343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000710

Gnomad ASJ AF: 0.000726

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000968

Gnomad OTH AF: 0.000639

GnomAD2 exomes AF: 0.000302 AC: 18 AN: 59550 AF XY: 0.000368

Gnomad AFR exome AF: 0.000355

Gnomad AMR exome AF: 0.000988

Gnomad ASJ exome AF: 0.000584

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000128

Gnomad OTH exome AF: 0.000502

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000115 AC: 162 AN: 1408130 Hom.: 0 Cov.: 33 AF XY: 0.000130 AC XY: 91 AN XY: 700946

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

African (AFR) AF: 0.000361 AC: 12 AN: 33210

American (AMR) AF: 0.000616 AC: 27 AN: 43866

Ashkenazi Jewish (ASJ) AF: 0.000519 AC: 13 AN: 25034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39076

South Asian (SAS) AF: 0.00 AC: 0 AN: 82626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40200

Middle Eastern (MID) AF: 0.00127 AC: 5 AN: 3944

European-Non Finnish (NFE) AF: 0.0000851 AC: 92 AN: 1081498

Other (OTH) AF: 0.000222 AC: 13 AN: 58676

⚠️ 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: 0.000239 AC: 28 AN: 117322 Hom.: 0 Cov.: 15 AF XY: 0.000229 AC XY: 13 AN XY: 56810

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

African (AFR) AF: 0.000342 AC: 12 AN: 35052

American (AMR) AF: 0.000709 AC: 8 AN: 11280

Ashkenazi Jewish (ASJ) AF: 0.000726 AC: 2 AN: 2756

East Asian (EAS) AF: 0.00 AC: 0 AN: 3280

South Asian (SAS) AF: 0.00 AC: 0 AN: 3326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000968 AC: 5 AN: 51656

Other (OTH) AF: 0.000631 AC: 1 AN: 1586

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000000333067), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000169 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.89
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.065
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.14
MutPred		0.31		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.17
ClinPred		0.073	T
Varity_R		0.26
gMVP		0.011
Mutation Taster		=97/3	polymorphism

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: rs1470327269; hg19: chr16-22545371;