3-175163656-C-T

Position:

• chr3-175163656-C-T

Variant summary

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

The ENST00000454872.6(NAALADL2):​c.545+66365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,856 control chromosomes in the GnomAD database, including 17,734 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 0.47 (17734 hom., cov: 32)
• Consequence: NAALADL2 ENST00000454872.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.545+66365C>T		intron_variant		ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.545+66365C>T		intron_variant		1	NM_207015.3	ENSP00000404705	P1
NAALADL2	ENST00000485853.5	n.631+66365C>T		intron_variant, non_coding_transcript_variant		1
NAALADL2	ENST00000473253.5	n.777+66365C>T		intron_variant, non_coding_transcript_variant		2
NAALADL2	ENST00000489299.5	n.236+39015C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71904 AN: 151736 Hom.: 17724 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.474 AC: 71944 AN: 151856 Hom.: 17734 Cov.: 32 AF XY: 0.476 AC XY: 35338 AN XY: 74204

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.462

Alfa AF: 0.498 Hom.: 2392

Bravo AF: 0.474

Asia WGS AF: 0.534 AC: 1856 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	0.38
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs1870740; hg19: chr3-174881446;