rs1381126

Variant names:

• chr3-175169065-G-A
• rs1381126
• NM_207015.3:c.546-64866G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207015.3(NAALADL2):​c.546-64866G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 151,568 control chromosomes in the GnomAD database, including 52,798 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 0.83 (52798 hom., cov: 31)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 2 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.546-64866G>A		intron_variant	Intron 2 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.546-64866G>A		intron_variant	Intron 2 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000485853.5	n.632-64866G>A		intron_variant	Intron 2 of 3	1
NAALADL2	ENST00000473253.5	n.778-64866G>A		intron_variant	Intron 2 of 10	2
NAALADL2	ENST00000489299.5	n.236+44424G>A		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126023 AN: 151450 Hom.: 52768 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.832

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.832 AC: 126107 AN: 151568 Hom.: 52798 Cov.: 31 AF XY: 0.832 AC XY: 61585 AN XY: 74060

African (AFR) AF: 0.732 AC: 30311 AN: 41398

American (AMR) AF: 0.878 AC: 13342 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2773 AN: 3466

East Asian (EAS) AF: 0.929 AC: 4800 AN: 5166

South Asian (SAS) AF: 0.860 AC: 4142 AN: 4816

European-Finnish (FIN) AF: 0.827 AC: 8733 AN: 10562

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.874 AC: 59102 AN: 67654

Other (OTH) AF: 0.830 AC: 1747 AN: 2104

Alfa AF: 0.853 Hom.: 7174

Bravo AF: 0.833

Asia WGS AF: 0.868 AC: 3014 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.19
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1381126; hg19: chr3-174886855;