chr3-174862218-G-A

Variant names:

• chr3-174862218-G-A
• rs10513723
• NM_207015.3:c.43+2768G>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.43+2768G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,946 control chromosomes in the GnomAD database, including 3,155 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 0.18 (3155 hom., cov: 31)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.43+2768G>A		intron_variant	Intron 1 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.43+2768G>A		intron_variant	Intron 1 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000485853.5	n.129+2768G>A		intron_variant	Intron 1 of 3	1
NAALADL2	ENST00000434257.1	c.-9+124472G>A		intron_variant	Intron 3 of 3	4		ENSP00000409858.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26894 AN: 151828 Hom.: 3142 Cov.: 31

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0990

Gnomad EAS AF: 0.0401

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.177 AC: 26942 AN: 151946 Hom.: 3155 Cov.: 31 AF XY: 0.176 AC XY: 13101 AN XY: 74294

African (AFR) AF: 0.324 AC: 13401 AN: 41412

American (AMR) AF: 0.117 AC: 1790 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0990 AC: 343 AN: 3464

East Asian (EAS) AF: 0.0402 AC: 208 AN: 5178

South Asian (SAS) AF: 0.0425 AC: 205 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2059 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8406 AN: 67932

Other (OTH) AF: 0.157 AC: 332 AN: 2108

Alfa AF: 0.132 Hom.: 884

Bravo AF: 0.177

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.57
PhyloP100		0.13
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: rs10513723; hg19: chr3-174580008;