4-88697328-C-T

Position:

chr4-88697328-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153757.4(NAP1L5):c.427G>A(p.Glu143Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,613,894 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

NAP1L5
NM_153757.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.75

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:

HERC3 (HGNC:):

HERC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035840273).

BP6

Variant 4-88697328-C-T is Benign according to our data. Variant chr4-88697328-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 773709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAP1L5	NM_153757.4 link	c.427G>A	p.Glu143Lys	missense_variant	1/1	ENST00000323061.7	NP_715638.1	Q96NT1
HERC3	NM_014606.3 link	c.2658-6770C>T		intron_variant		ENST00000402738.6	NP_055421.1	Q15034-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NAP1L5	ENST00000323061.7 link	c.427G>A	p.Glu143Lys	missense_variant	1/1	6	NM_153757.4	ENSP00000320488.5	Q96NT1
HERC3	ENST00000402738.6 link	c.2658-6770C>T		intron_variant		1	NM_014606.3	ENSP00000385684.1	Q15034-1
HERC3	ENST00000264345.7 link	c.2658-6770C>T		intron_variant		1			Q15034-1
HERC3	ENST00000512194.2 link	c.2634-6770C>T		intron_variant		5		ENSP00000421021.2	H0Y8G9

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

365

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00270

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00196

AC:

490

AN:

250528

Hom.:

AF XY:

0.00207

AC XY:

280

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00298

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00198

AC:

2892

AN:

1461716

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

1496

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.00406

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00213

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00240

AC:

365

AN:

152178

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00271

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00265

Hom.:

Bravo

AF:

0.00303

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00182

AC:

ExAC

AF:

0.00208

AC:

252

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.081

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.47

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.3

REVEL

Benign

0.044

Sift

Benign

0.32

Sift4G

Pathogenic

0.0

Polyphen

0.86

Vest4

0.23

MVP

0.21

MPC

0.30

ClinPred

0.0087

GERP RS

0.94

Varity_R

0.12

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over