rs667269

chr3-174621815-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000489729.5(NAALADL2):n.178+71178A>G variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NAALADL2	XM_006713560.4	c.-115+71178A>G		intron_variant
NAALADL2	XM_017006071.2	c.-185+71178A>G		intron_variant
NAALADL2	XM_017006073.2	c.-198-70158A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAALADL2	ENST00000489729.5	n.178+71178A>G		intron_variant, non_coding_transcript_variant		1
NAALADL2	ENST00000491329.5	n.171-70158A>G		intron_variant, non_coding_transcript_variant		1
NAALADL2	ENST00000434257.1	c.-115+71178A>G		intron_variant		4

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

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0513

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.169

Alfa AF: 0.156 Hom.: 655

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs667269; hg19: chr3-174339605;