rs667269

Variant names:

• chr3-174621815-A-G
• rs667269
• ENST00000489729.5:n.178+71178A>G

Variant summary

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

The ENST00000434257.1(NAALADL2):​c.-115+71178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,162 control chromosomes in the GnomAD database, including 3,148 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 (3148 hom., cov: 32)
• Consequence: NAALADL2 ENST00000434257.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434257.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	ENST00000489729.5	TSL:1	n.178+71178A>G		intron	N/A
	NAALADL2	ENST00000491329.5	TSL:1	n.171-70158A>G		intron	N/A
	NAALADL2	ENST00000434257.1	TSL:4	c.-115+71178A>G		intron	N/A	ENSP00000409858.1	C9JQ86

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27880 AN: 152046 Hom.: 3141 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.184 AC: 27927 AN: 152162 Hom.: 3148 Cov.: 32 AF XY: 0.181 AC XY: 13470 AN XY: 74408

African (AFR) AF: 0.314 AC: 13037 AN: 41480

American (AMR) AF: 0.127 AC: 1942 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3468

East Asian (EAS) AF: 0.0513 AC: 266 AN: 5184

South Asian (SAS) AF: 0.171 AC: 827 AN: 4832

European-Finnish (FIN) AF: 0.122 AC: 1298 AN: 10602

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9643 AN: 67986

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.159 Hom.: 816

Bravo AF: 0.187

Asia WGS AF: 0.161 AC: 559 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	1.4
DANN	Benign	0.69
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs667269;

hg19: chr3-174339605;