Variant 2-241815120-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001167600.3(NEU4):c.430G>A(p.Glu144Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00756 in 1,572,716 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0078 ( 61 hom. )

Consequence

NEU4
NM_001167600.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.445

Variant links:

Genes affected

NEU4 (HGNC:21328): (neuraminidase 4) The protein encoded by this gene belongs to a family of glycohydrolytic enzymes, which remove terminal sialic acid residues from various sialo derivatives, such as glycoproteins, glycolipids, oligosaccharides, and gangliosides. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Nov 2009]

NEU4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006876141).

BP6

Variant 2-241815120-G-A is Benign according to our data. Variant chr2-241815120-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652118.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEU4	NM_001167600.3 linkuse as main transcript	c.430G>A	p.Glu144Lys	missense_variant	3/4	ENST00000407683.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEU4	ENST00000407683.6 linkuse as main transcript	c.430G>A	p.Glu144Lys	missense_variant	3/4	2	NM_001167600.3	P2	Q8WWR8-1

Frequencies

GnomAD3 genomes

AF:

0.00538

AC:

818

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00892

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00623

AC:

1286

AN:

206574

Hom.:

AF XY:

0.00633

AC XY:

726

AN XY:

114718

show subpopulations

Gnomad AFR exome

AF:

0.00108

Gnomad AMR exome

AF:

0.00297

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00227

Gnomad FIN exome

AF:

0.00718

Gnomad NFE exome

AF:

0.00971

Gnomad OTH exome

AF:

0.00515

GnomAD4 exome

AF:

0.00779

AC:

11065

AN:

1420430

Hom.:

Cov.:

AF XY:

0.00762

AC XY:

5355

AN XY:

703008

show subpopulations

Gnomad4 AFR exome

AF:

0.00118

Gnomad4 AMR exome

AF:

0.00340

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0000517

Gnomad4 SAS exome

AF:

0.00196

Gnomad4 FIN exome

AF:

0.00816

Gnomad4 NFE exome

AF:

0.00887

Gnomad4 OTH exome

AF:

0.00676

GnomAD4 genome

AF:

0.00537

AC:

818

AN:

152286

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

373

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00631

Gnomad4 NFE

AF:

0.00893

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00889

Hom.:

Bravo

AF:

0.00518

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.000986

AC:

ESP6500EA

AF:

0.00761

AC:

ExAC

AF:

0.00603

AC:

718

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

NEU4: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.65

D;D;.;.;D;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.30

MetaRNN

Benign

0.0069

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

L;L;.;.;L;.;.

MutationTaster

Benign

0.88

N;N;N;N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.1

N;N;N;N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.12

T;T;T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T;T;T

Polyphen

0.59

P;P;.;B;P;.;.

Vest4

0.24

MVP

0.19

MPC

0.057

ClinPred

0.0061

GERP RS

2.6

Varity_R

0.10

gMVP

0.47

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