Variant chr3-175097119-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_207015.3(NAALADL2):c.373G>A(p.Val125Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,613,652 control chromosomes in the GnomAD database, including 48 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 (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 47 hom. )

Consequence

NAALADL2
NM_207015.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.118

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:

NAALADL2-AS3 (HGNC:41014): (NAALADL2 antisense RNA 3)

NAALADL2-AS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059213936).

BP6

Variant 3-175097119-G-A is Benign according to our data. Variant chr3-175097119-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654282.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00484 (7080/1461472) while in subpopulation MID AF= 0.0205 (118/5766). AF 95% confidence interval is 0.0175. There are 47 homozygotes in gnomad4_exome. There are 3614 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALADL2	NM_207015.3 linkuse as main transcript	c.373G>A	p.Val125Ile	missense_variant	2/14	ENST00000454872.6	NP_996898.2
NAALADL2-AS3	NR_046390.1 linkuse as main transcript	n.110+15425C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6 linkuse as main transcript	c.373G>A	p.Val125Ile	missense_variant	2/14	1	NM_207015.3	ENSP00000404705	P1	Q58DX5-1
NAALADL2-AS3	ENST00000453180.5 linkuse as main transcript	n.110+15425C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

409

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00706

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00431

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00374

AC:

932

AN:

248914

Hom.:

AF XY:

0.00415

AC XY:

561

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.000775

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.000994

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00843

Gnomad FIN exome

AF:

0.000975

Gnomad NFE exome

AF:

0.00479

Gnomad OTH exome

AF:

0.00431

GnomAD4 exome

AF:

0.00484

AC:

7080

AN:

1461472

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

3614

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00846

Gnomad4 FIN exome

AF:

0.000768

Gnomad4 NFE exome

AF:

0.00519

Gnomad4 OTH exome

AF:

0.00484

GnomAD4 genome

AF:

0.00267

AC:

406

AN:

152180

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

196

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000867

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00665

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00431

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00415

Hom.:

Bravo

AF:

0.00278

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.00163

AC:

ESP6500EA

AF:

0.00427

AC:

ExAC

AF:

0.00376

AC:

454

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00524

EpiControl

AF:

0.00569

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

May 01, 2023

NAALADL2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.00058

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.20

M_CAP

Benign

0.0045

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.77

N;N

REVEL

Benign

0.015

Sift

Benign

0.77

T;T

Sift4G

Benign

0.85

T;T

Polyphen

0.0

.;B

Vest4

0.055

MVP

0.25

MPC

0.0055

ClinPred

0.00069

GERP RS

0.72

Varity_R

0.022

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