Genetic Variant NM_153757.4:c.504A>T (chr4-88697251-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_153757.4(NAP1L5):c.504A>T(p.Lys168Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NAP1L5
NM_153757.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.158

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:

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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=0.08550125).

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.504A>T	p.Lys168Asn	missense	Exon 1 of 1	NP_715638.1	Q96NT1
HERC3	NM_014606.3	MANE Select	c.2658-6847T>A		intron	N/A	NP_055421.1	Q15034-1
HERC3	NM_001375480.1		c.2655-6847T>A		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.504A>T	p.Lys168Asn	missense	Exon 1 of 1	ENSP00000320488.5	Q96NT1
HERC3	ENST00000402738.6	TSL:1 MANE Select	c.2658-6847T>A		intron	N/A	ENSP00000385684.1	Q15034-1
HERC3	ENST00000512194.2	TSL:5	c.2634-6847T>A		intron	N/A	ENSP00000421021.2	H0Y8G9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

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

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.059

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.28

M_CAP

Benign

0.0050

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

-0.16

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.7

REVEL

Benign

0.011

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.020

Polyphen

0.069

Vest4

0.24

MutPred

0.36

Loss of ubiquitination at K168 (P = 0.0077)

MVP

0.068

MPC

0.31

ClinPred

0.099

GERP RS

0.16

Varity_R

0.17

gMVP

0.050

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over