rs17533447

chr3-175260962-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAALADL2	NM_207015.3	c.939+4432G>A		intron_variant		ENST00000454872.6
NAALADL2-AS2	NR_046713.1	n.40+10095C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAALADL2	ENST00000454872.6	c.939+4432G>A		intron_variant		1	NM_207015.3	P1
NAALADL2-AS2	ENST00000424690.1	n.40+10095C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0370

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.137

Alfa AF: 0.163 Hom.: 2883

Bravo AF: 0.123

Asia WGS AF: 0.161 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.84
Dann	Benign	0.71

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

LitVar

Other links and lift over

dbSNP: rs17533447; hg19: chr3-174978751;