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 ENST00000489729.5(NAALADL2):​n.178+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 ENST00000489729.5 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	XM_006713560.4	c.-115+71178A>G		intron_variant	Intron 2 of 15		XP_006713623.1
NAALADL2	XM_017006071.2	c.-185+71178A>G		intron_variant	Intron 4 of 18		XP_016861560.1
NAALADL2	XM_017006073.2	c.-198-70158A>G		intron_variant	Intron 3 of 17		XP_016861562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000489729.5	n.178+71178A>G		intron_variant	Intron 3 of 3	1
NAALADL2	ENST00000491329.5	n.171-70158A>G		intron_variant	Intron 2 of 3	1
NAALADL2	ENST00000434257.1	c.-115+71178A>G		intron_variant	Intron 2 of 3	4		ENSP00000409858.1

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 v4.3

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

Other links and lift over

dbSNP: rs667269; hg19: chr3-174339605;