chr4-88697282-T-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153757.4(NAP1L5):c.473A>C(p.Glu158Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,539,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

NAP1L5
NM_153757.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

Publications

0 publications found

Variant links:

Genes affected

NAP1L5 (HGNC:19968): (nucleosome assembly protein 1 like 5) This gene encodes a protein that shares sequence similarity to nucleosome assembly factors, but may be localized to the cytoplasm rather than the nucleus. Expression of this gene is downregulated in hepatocellular carcinomas. This gene is located within a differentially methylated region (DMR) and is imprinted and paternally expressed. There is a related pseudogene on chromosome 4. [provided by RefSeq, Nov 2015]

NAP1L5 links:

HERC3 (HGNC:4876): (HECT and RLD domain containing E3 ubiquitin protein ligase 3) This gene encodes a member the HERC ubiquitin ligase family. The encoded protein is located in the cytosol and binds ubiquitin via a HECT domain. Mutations in this gene have been associated with colorectal and gastric carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

HERC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09439555).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153757.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAP1L5	NM_153757.4	MANE Select	c.473A>C	p.Glu158Ala	missense	Exon 1 of 1	NP_715638.1	Q96NT1
HERC3	NM_014606.3	MANE Select	c.2658-6816T>G		intron	N/A	NP_055421.1	Q15034-1
HERC3	NM_001375480.1		c.2655-6816T>G		intron	N/A	NP_001362409.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAP1L5	ENST00000323061.7	TSL:6 MANE Select	c.473A>C	p.Glu158Ala	missense	Exon 1 of 1	ENSP00000320488.5	Q96NT1
HERC3	ENST00000402738.6	TSL:1 MANE Select	c.2658-6816T>G		intron	N/A	ENSP00000385684.1	Q15034-1
HERC3	ENST00000512194.2	TSL:5	c.2634-6816T>G		intron	N/A	ENSP00000421021.2	H0Y8G9

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151748

Hom.:

Cov.:

show subpopulations

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000186

AC:

AN:

214724

AF XY:

0.0000260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000356

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000301

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1388004

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

686588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31064

American (AMR)

AF:

0.0000269

AC:

AN:

37210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23002

East Asian (EAS)

AF:

0.00

AC:

AN:

37620

South Asian (SAS)

AF:

0.0000134

AC:

AN:

74602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5468

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

1071100

Other (OTH)

AF:

0.00

AC:

AN:

56984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

AF:

0.0000132

AC:

AN:

151748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74086

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41356

American (AMR)

AF:

0.00

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67894

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.098

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.33

M_CAP

Benign

0.0023

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

2.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.99

REVEL

Benign

0.031

Sift

Benign

0.030

Sift4G

Pathogenic

0.0

Polyphen

0.62

Vest4

0.24

MutPred

0.32

Loss of helix (P = 0.5774)

MVP

0.093

MPC

0.28

ClinPred

0.10

GERP RS

1.7

Varity_R

0.048

gMVP

0.10

Mutation Taster

=88/12

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over