rs12493995

Positions:

• chr3-174684796-C-T

Variant summary

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

The ENST00000489729.5(NAALADL2):​n.179-52845C>T 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 0.0796 in 151,966 control chromosomes in the GnomAD database, including 697 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 0.080 (697 hom., cov: 31)
• Consequence: NAALADL2 ENST00000489729.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALADL2	XM_006713560.4	c.-114-52845C>T		intron_variant			XP_006713623.1
NAALADL2	XM_017006071.2	c.-184-50090C>T		intron_variant			XP_016861560.1
NAALADL2	XM_017006073.2	c.-198-7177C>T		intron_variant			XP_016861562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000489729.5	n.179-52845C>T		intron_variant, non_coding_transcript_variant		1
NAALADL2	ENST00000491329.5	n.171-7177C>T		intron_variant, non_coding_transcript_variant		1
NAALADL2	ENST00000434257.1	c.-114-52845C>T		intron_variant		4		ENSP00000409858

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12101 AN: 151846 Hom.: 700 Cov.: 31

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.0462

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0553

Gnomad OTH AF: 0.0795

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

GnomAD4 genome AF: 0.0796 AC: 12096 AN: 151966 Hom.: 697 Cov.: 31 AF XY: 0.0846 AC XY: 6283 AN XY: 74278

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.0462

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.0534

Gnomad4 NFE AF: 0.0553

Gnomad4 OTH AF: 0.0782

Alfa AF: 0.0728 Hom.: 327

Bravo AF: 0.0789

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.53
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12493995; hg19: chr3-174402586;