rs150099163

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 16/22 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

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2654282.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 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 GnomAdExome4. There are 3614 alleles in the male GnomAdExome4 subpopulation. Median coverage is 35. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 47 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207015.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	NM_207015.3	MANE Select	c.373G>A	p.Val125Ile	missense	Exon 2 of 14	NP_996898.2	Q58DX5-1
	NAALADL2-AS3	NR_046390.1		n.110+15425C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAALADL2	ENST00000454872.6	TSL:1 MANE Select	c.373G>A	p.Val125Ile	missense	Exon 2 of 14	ENSP00000404705.1	Q58DX5-1
NAALADL2	ENST00000485853.5	TSL:1	n.459G>A		non_coding_transcript_exon	Exon 2 of 4
NAALADL2	ENST00000434257.1	TSL:4	c.322G>A	p.Val108Ile	missense	Exon 4 of 4	ENSP00000409858.1	C9JQ86

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

GnomAD2 exomes

AF:

0.00374

AC:

932

AN:

248914

AF XY:

0.00415

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 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

African (AFR)

AF:

0.000657

AC:

AN:

33474

American (AMR)

AF:

0.00181

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000957

AC:

AN:

26128

East Asian (EAS)

AF:

0.000101

AC:

AN:

39698

South Asian (SAS)

AF:

0.00846

AC:

730

AN:

86252

European-Finnish (FIN)

AF:

0.000768

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.0205

AC:

118

AN:

5766

European-Non Finnish (NFE)

AF:

0.00519

AC:

5767

AN:

1111672

Other (OTH)

AF:

0.00484

AC:

292

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

345

690

1034

1379

1724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

228

456

684

912

1140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00267

AC:

406

AN:

152180

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

196

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.000867

AC:

AN:

41534

American (AMR)

AF:

0.00138

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00665

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00431

AC:

293

AN:

68008

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00405

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.00058

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.20

M_CAP

Benign

0.0045

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

0.12

PrimateAI

Benign

0.36

PROVEAN

Benign

0.77

REVEL

Benign

0.015

Sift

Benign

0.77

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.055

MVP

0.25

MPC

0.0055

ClinPred

0.00069

GERP RS

0.72

Varity_R

0.022

gMVP

0.21

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over