rs9881727

chr3-175144195-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207015.3(NAALADL2):c.545+46904T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,496 control chromosomes in the GnomAD database, including 8,945 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 0.34 (8945 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAALADL2	NM_207015.3	c.545+46904T>C		intron_variant		ENST00000454872.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAALADL2	ENST00000454872.6	c.545+46904T>C		intron_variant		1	NM_207015.3	P1
NAALADL2	ENST00000485853.5	n.631+46904T>C		intron_variant, non_coding_transcript_variant		1
NAALADL2	ENST00000473253.5	n.777+46904T>C		intron_variant, non_coding_transcript_variant		2
NAALADL2	ENST00000489299.5	n.236+19554T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 51963 AN: 151376 Hom.: 8930 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.343 AC: 52014 AN: 151496 Hom.: 8945 Cov.: 32 AF XY: 0.339 AC XY: 25082 AN XY: 74036

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.367

Alfa AF: 0.349 Hom.: 1134

Bravo AF: 0.347

Asia WGS AF: 0.344 AC: 1190 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.0
Dann	Benign	0.43

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: rs9881727; hg19: chr3-174861985;