chr3-175447413-T-G

Variant names:

• chr3-175447413-T-G
• rs2161041
• NM_207015.3:c.1234+41T>G

Variant summary

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

The NM_207015.3(NAALADL2):​c.1234+41T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,409,842 control chromosomes in the GnomAD database, including 478,711 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 0.80 (49396 hom., cov: 32)
  • Exomes 𝑓: 0.83 (429315 hom.)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 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.1234+41T>G		intron	N/A	NP_996898.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	ENST00000454872.6	TSL:1 MANE Select	c.1234+41T>G		intron	N/A	ENSP00000404705.1
	NAALADL2	ENST00000414826.1	TSL:1	n.*99+41T>G		intron	N/A	ENSP00000396969.1
	NAALADL2	ENST00000473253.5	TSL:2	n.1466+41T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122190 AN: 152012 Hom.: 49369 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.868

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.836

GnomAD2 exomes AF: 0.842 AC: 89140 AN: 105814 AF XY: 0.846

Gnomad AFR exome AF: 0.720

Gnomad AMR exome AF: 0.866

Gnomad ASJ exome AF: 0.882

Gnomad EAS exome AF: 0.966

Gnomad FIN exome AF: 0.838

Gnomad NFE exome AF: 0.828

Gnomad OTH exome AF: 0.846

GnomAD4 exome AF: 0.825 AC: 1037980 AN: 1257710 Hom.: 429315 Cov.: 17 AF XY: 0.827 AC XY: 514321 AN XY: 621792

African (AFR) AF: 0.711 AC: 19540 AN: 27490

American (AMR) AF: 0.860 AC: 17913 AN: 20840

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 17925 AN: 20322

East Asian (EAS) AF: 0.948 AC: 33286 AN: 35094

South Asian (SAS) AF: 0.849 AC: 55613 AN: 65508

European-Finnish (FIN) AF: 0.835 AC: 38775 AN: 46422

Middle Eastern (MID) AF: 0.893 AC: 4663 AN: 5220

European-Non Finnish (NFE) AF: 0.819 AC: 806567 AN: 984222

Other (OTH) AF: 0.831 AC: 43698 AN: 52592

GnomAD4 genome AF: 0.804 AC: 122269 AN: 152132 Hom.: 49396 Cov.: 32 AF XY: 0.808 AC XY: 60044 AN XY: 74352

African (AFR) AF: 0.716 AC: 29728 AN: 41500

American (AMR) AF: 0.857 AC: 13087 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3046 AN: 3472

East Asian (EAS) AF: 0.959 AC: 4960 AN: 5170

South Asian (SAS) AF: 0.849 AC: 4089 AN: 4818

European-Finnish (FIN) AF: 0.841 AC: 8906 AN: 10590

Middle Eastern (MID) AF: 0.862 AC: 250 AN: 290

European-Non Finnish (NFE) AF: 0.821 AC: 55801 AN: 67990

Other (OTH) AF: 0.838 AC: 1773 AN: 2116

Alfa AF: 0.778 Hom.: 18619

Bravo AF: 0.802

Asia WGS AF: 0.894 AC: 3107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.078
DANN	Benign	0.65
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2161041; hg19: chr3-175165201;