Variant 3-175234070-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207015.3(NAALADL2):c.685A>G(p.Ser229Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NAALADL2
NM_207015.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06470981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALADL2	NM_207015.3 linkuse as main transcript	c.685A>G	p.Ser229Gly	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.685A>G	p.Ser229Gly	missense_variant	3/14	1	NM_207015.3	ENSP00000404705	P1	Q58DX5-1
NAALADL2	ENST00000485853.5 linkuse as main transcript	n.771A>G		non_coding_transcript_exon_variant	3/4	1
NAALADL2	ENST00000473253.5 linkuse as main transcript	n.917A>G		non_coding_transcript_exon_variant	3/11	2
NAALADL2	ENST00000489299.5 linkuse as main transcript	n.424A>G		non_coding_transcript_exon_variant	3/11	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000322

AC:

AN:

248814

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134952

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000232

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:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461642

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2021

The c.685A>G (p.S229G) alteration is located in exon 3 (coding exon 3) of the NAALADL2 gene. This alteration results from a A to G substitution at nucleotide position 685, causing the serine (S) at amino acid position 229 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.79

M_CAP

Benign

0.0090

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.92

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

REVEL

Benign

0.015

Sift

Benign

0.25

Sift4G

Benign

0.21

Polyphen

0.0010

Vest4

0.10

MutPred

0.30

Loss of sheet (P = 0.0126);

MVP

0.48

MPC

0.0054

ClinPred

0.21

GERP RS

4.4

Varity_R

0.061

gMVP

0.50

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

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