3-175337970-T-G

Variant names:

• chr3-175337970-T-G
• rs2042126
• NM_207015.3:c.1090+13645T>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.1090+13645T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,972 control chromosomes in the GnomAD database, including 15,164 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 0.43 (15164 hom., cov: 31)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	NM_207015.3	MANE Select	c.1090+13645T>G		intron	N/A	NP_996898.2	Q58DX5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	ENST00000454872.6	TSL:1 MANE Select	c.1090+13645T>G		intron	N/A	ENSP00000404705.1	Q58DX5-1
	NAALADL2	ENST00000414826.1	TSL:1	n.120+81440T>G		intron	N/A	ENSP00000396969.1	Q6H9J7
	NAALADL2	ENST00000473253.5	TSL:2	n.1322+13645T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65247 AN: 151854 Hom.: 15153 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.430 AC: 65283 AN: 151972 Hom.: 15164 Cov.: 31 AF XY: 0.436 AC XY: 32383 AN XY: 74252

African (AFR) AF: 0.276 AC: 11468 AN: 41506

American (AMR) AF: 0.527 AC: 8031 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3468

East Asian (EAS) AF: 0.705 AC: 3624 AN: 5142

South Asian (SAS) AF: 0.567 AC: 2732 AN: 4820

European-Finnish (FIN) AF: 0.529 AC: 5576 AN: 10546

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.464 AC: 31534 AN: 67934

Other (OTH) AF: 0.425 AC: 896 AN: 2106

Alfa AF: 0.437 Hom.: 12984

Bravo AF: 0.423

Asia WGS AF: 0.588 AC: 2043 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	0.52
DANN	Benign	0.37
PhyloP100		-0.56
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: rs2042126; hg19: chr3-175055759;