Genetic Variant NAALADL2:c.1234+41T>G (chr3-175447413-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_207015.3(NAALADL2):c.1234+41T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,409,842 control chromosomes in the GnomAD database, including 478,711 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 49396 hom., cov: 32)

Exomes 𝑓: 0.83 ( 429315 hom. )

Consequence

NAALADL2
NM_207015.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

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.1234+41T>G		intron	N/A	NP_996898.2	Q58DX5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAALADL2	ENST00000454872.6	TSL:1 MANE Select	c.1234+41T>G	intron	N/A	ENSP00000404705.1	Q58DX5-1
NAALADL2	ENST00000414826.1	TSL:1	n.*99+41T>G	intron	N/A	ENSP00000396969.1	Q6H9J7
NAALADL2	ENST00000473253.5	TSL:2	n.1466+41T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

122190

AN:

152012

Hom.:

49369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.690

Gnomad AMR

AF:

0.857

Gnomad ASJ

AF:

0.877

Gnomad EAS

AF:

0.959

Gnomad SAS

AF:

0.849

Gnomad FIN

AF:

0.841

Gnomad MID

AF:

0.868

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.836

GnomAD2 exomes

AF:

0.842

AC:

89140

AN:

105814

AF XY:

0.846

show subpopulations

Gnomad AFR exome

AF:

0.720

Gnomad AMR exome

AF:

0.866

Gnomad ASJ exome

AF:

0.882

Gnomad EAS exome

AF:

0.966

Gnomad FIN exome

AF:

0.838

Gnomad NFE exome

AF:

0.828

Gnomad OTH exome

AF:

0.846

GnomAD4 exome

AF:

0.825

AC:

1037980

AN:

1257710

Hom.:

429315

Cov.:

AF XY:

0.827

AC XY:

514321

AN XY:

621792

show subpopulations

African (AFR)

AF:

0.711

AC:

19540

AN:

27490

American (AMR)

AF:

0.860

AC:

17913

AN:

20840

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

17925

AN:

20322

East Asian (EAS)

AF:

0.948

AC:

33286

AN:

35094

South Asian (SAS)

AF:

0.849

AC:

55613

AN:

65508

European-Finnish (FIN)

AF:

0.835

AC:

38775

AN:

46422

Middle Eastern (MID)

AF:

0.893

AC:

4663

AN:

5220

European-Non Finnish (NFE)

AF:

0.819

AC:

806567

AN:

984222

Other (OTH)

AF:

0.831

AC:

43698

AN:

52592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

7873

15746

23619

31492

39365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18690

37380

56070

74760

93450

<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:

0.804

AC:

122269

AN:

152132

Hom.:

49396

Cov.:

AF XY:

0.808

AC XY:

60044

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.716

AC:

29728

AN:

41500

American (AMR)

AF:

0.857

AC:

13087

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.877

AC:

3046

AN:

3472

East Asian (EAS)

AF:

0.959

AC:

4960

AN:

5170

South Asian (SAS)

AF:

0.849

AC:

4089

AN:

4818

European-Finnish (FIN)

AF:

0.841

AC:

8906

AN:

10590

Middle Eastern (MID)

AF:

0.862

AC:

250

AN:

290

European-Non Finnish (NFE)

AF:

0.821

AC:

55801

AN:

67990

Other (OTH)

AF:

0.838

AC:

1773

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1197

2395

3592

4790

5987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<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:

0.778

Hom.:

18619

Bravo

AF:

0.802

Asia WGS

AF:

0.894

AC:

3107

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.078

(source)

DANN

Benign

0.65

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over