Genetic Variant NPIPA5:p.Pro321Gln (chr16-15363750-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001277325.2(NPIPA5):c.962C>A(p.Pro321Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P321L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 24)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NPIPA5
NM_001277325.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

1 publications found

Variant links:

Genes affected

NPIPA5 (HGNC:41980): (nuclear pore complex interacting protein family member A5) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPIPA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20174024).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277325.2. 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
	NPIPA5	NM_001277325.2	MANE Select	c.962C>A	p.Pro321Gln	missense	Exon 8 of 8	NP_001264254.1	E9PKD4-1
	NPIPA5	NM_001351200.1		c.*333C>A		3_prime_UTR	Exon 9 of 9	NP_001338129.1	E9PKD4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPIPA5	ENST00000360151.9	TSL:1 MANE Select	c.962C>A	p.Pro321Gln	missense	Exon 8 of 8	ENSP00000433597.1	E9PKD4-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

125900

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.75e-7

AC:

AN:

1290814

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

641302

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

30548

American (AMR)

AF:

0.00

AC:

AN:

34668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21464

East Asian (EAS)

AF:

0.00

AC:

AN:

25610

South Asian (SAS)

AF:

0.00

AC:

AN:

78174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3544

European-Non Finnish (NFE)

AF:

9.87e-7

AC:

AN:

1012872

Other (OTH)

AF:

0.00

AC:

AN:

51198

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

125900

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

60522

African (AFR)

AF:

0.00

AC:

AN:

35232

American (AMR)

AF:

0.00

AC:

AN:

11526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3004

East Asian (EAS)

AF:

0.00

AC:

AN:

2552

South Asian (SAS)

AF:

0.00

AC:

AN:

3672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

256

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59472

Other (OTH)

AF:

0.00

AC:

AN:

1730

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.082

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.45

M_CAP

Benign

0.012

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

PhyloP100

0.0

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Vest4

0.17

MutPred

0.48

Loss of glycosylation at P321 (P = 0.0143)

MVP

0.082

MPC

1.9

ClinPred

0.47

Varity_R

0.13

gMVP

0.012

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over