Variant 4-88697686-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_153757.4(NAP1L5):c.69A>G(p.Ala23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,611,472 control chromosomes in the GnomAD database, including 137,356 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 18094 hom., cov: 32)

Exomes 𝑓: 0.40 ( 119262 hom. )

Consequence

NAP1L5
NM_153757.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.927

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-0.927 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAP1L5	NM_153757.4 linkuse as main transcript	c.69A>G	p.Ala23=	synonymous_variant	1/1	ENST00000323061.7	NP_715638.1
HERC3	NM_014606.3 linkuse as main transcript	c.2658-6412T>C		intron_variant		ENST00000402738.6	NP_055421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAP1L5	ENST00000323061.7 linkuse as main transcript	c.69A>G	p.Ala23=	synonymous_variant	1/1		NM_153757.4	ENSP00000320488	P1
HERC3	ENST00000402738.6 linkuse as main transcript	c.2658-6412T>C		intron_variant		1	NM_014606.3	ENSP00000385684	P1	Q15034-1
HERC3	ENST00000264345.7 linkuse as main transcript	c.2658-6412T>C		intron_variant		1		ENSP00000264345	P1	Q15034-1

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71414

AN:

151790

Hom.:

18054

Cov.:

show subpopulations

Gnomad AFR

AF:

0.656

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.598

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.435

GnomAD3 exomes

AF:

0.431

AC:

105180

AN:

243920

Hom.:

24106

AF XY:

0.432

AC XY:

57567

AN XY:

133168

show subpopulations

Gnomad AFR exome

AF:

0.674

Gnomad AMR exome

AF:

0.387

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.549

Gnomad SAS exome

AF:

0.583

Gnomad FIN exome

AF:

0.450

Gnomad NFE exome

AF:

0.361

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.395

AC:

577092

AN:

1459564

Hom.:

119262

Cov.:

AF XY:

0.399

AC XY:

289502

AN XY:

726138

show subpopulations

Gnomad4 AFR exome

AF:

0.674

Gnomad4 AMR exome

AF:

0.393

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.594

Gnomad4 SAS exome

AF:

0.574

Gnomad4 FIN exome

AF:

0.444

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.418

GnomAD4 genome

AF:

0.471

AC:

71504

AN:

151908

Hom.:

18094

Cov.:

AF XY:

0.478

AC XY:

35506

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.656

Gnomad4 AMR

AF:

0.437

Gnomad4 ASJ

AF:

0.290

Gnomad4 EAS

AF:

0.562

Gnomad4 SAS

AF:

0.596

Gnomad4 FIN

AF:

0.451

Gnomad4 NFE

AF:

0.364

Gnomad4 OTH

AF:

0.442

Alfa

AF:

0.353

Hom.:

4993

Bravo

AF:

0.472

Asia WGS

AF:

0.639

AC:

2221

AN:

3478

EpiCase

AF:

0.358

EpiControl

AF:

0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over