Variant chr3-175233944-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_207015.3(NAALADL2):c.559C>G(p.Leu187Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,576,484 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000092 ( 1 hom. )

Consequence

NAALADL2
NM_207015.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.881

Variant links:

Genes affected

NAALADL2 (HGNC:23219): (N-acetylated alpha-linked acidic dipeptidase like 2) Predicted to enable metalloexopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within response to bacterium. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NAALADL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0078059435).

BP6

Variant 3-175233944-C-G is Benign according to our data. Variant chr3-175233944-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3050700.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALADL2	NM_207015.3 linkuse as main transcript	c.559C>G	p.Leu187Val	missense_variant	3/14	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6 linkuse as main transcript	c.559C>G	p.Leu187Val	missense_variant	3/14	1	NM_207015.3	ENSP00000404705	P1	Q58DX5-1
NAALADL2	ENST00000485853.5 linkuse as main transcript	n.645C>G		non_coding_transcript_exon_variant	3/4	1
NAALADL2	ENST00000473253.5 linkuse as main transcript	n.791C>G		non_coding_transcript_exon_variant	3/11	2
NAALADL2	ENST00000489299.5 linkuse as main transcript	n.298C>G		non_coding_transcript_exon_variant	3/11	2

Frequencies

GnomAD3 genomes

AF:

0.000763

AC:

116

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000206

AC:

AN:

237614

Hom.:

AF XY:

0.000124

AC XY:

AN XY:

128746

show subpopulations

Gnomad AFR exome

AF:

0.00275

Gnomad AMR exome

AF:

0.000187

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.0000920

AC:

131

AN:

1424266

Hom.:

Cov.:

AF XY:

0.0000747

AC XY:

AN XY:

709198

show subpopulations

Gnomad4 AFR exome

AF:

0.00337

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.22e-7

Gnomad4 OTH exome

AF:

0.000255

GnomAD4 genome

AF:

0.000762

AC:

116

AN:

152218

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000279

Hom.:

Bravo

AF:

0.000952

ESP6500AA

AF:

0.00333

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000232

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NAALADL2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 20, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0014

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.55

M_CAP

Benign

0.0067

MetaRNN

Benign

0.0078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.98

REVEL

Benign

0.051

Sift

Benign

0.058

Sift4G

Benign

0.17

Polyphen

0.0030

Vest4

0.15

MVP

0.22

MPC

0.0055

ClinPred

0.0048

GERP RS

2.6

Varity_R

0.072

gMVP

0.43

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