rs17533447

Variant names:

• chr3-175260962-G-A
• rs17533447
• NM_207015.3:c.939+4432G>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.939+4432G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,986 control chromosomes in the GnomAD database, including 1,503 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 0.13 (1503 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 3 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]

NAALADL2-AS2 (HGNC:41015): (NAALADL2 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	NM_207015.3	MANE Select	c.939+4432G>A		intron	N/A	NP_996898.2
	NAALADL2-AS2	NR_046713.1		n.40+10095C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	ENST00000454872.6	TSL:1 MANE Select	c.939+4432G>A		intron	N/A	ENSP00000404705.1
	NAALADL2	ENST00000414826.1	TSL:1	n.120+4432G>A		intron	N/A	ENSP00000396969.1
	NAALADL2-AS2	ENST00000424690.1	TSL:5	n.40+10095C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19589 AN: 151868 Hom.: 1501 Cov.: 32

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.129 AC: 19587 AN: 151986 Hom.: 1503 Cov.: 32 AF XY: 0.127 AC XY: 9417 AN XY: 74286

African (AFR) AF: 0.0370 AC: 1536 AN: 41494

American (AMR) AF: 0.134 AC: 2048 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3466

East Asian (EAS) AF: 0.153 AC: 784 AN: 5136

South Asian (SAS) AF: 0.135 AC: 652 AN: 4814

European-Finnish (FIN) AF: 0.150 AC: 1590 AN: 10572

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11986 AN: 67934

Other (OTH) AF: 0.137 AC: 288 AN: 2104

Alfa AF: 0.159 Hom.: 3470

Bravo AF: 0.123

Asia WGS AF: 0.161 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.84
DANN	Benign	0.71
PhyloP100		-0.51
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: rs17533447; hg19: chr3-174978751;