3-175186617-C-T

Variant names:

• chr3-175186617-C-T
• rs2861999
• NM_207015.3:c.546-47314C>T

Variant summary

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

The NM_207015.3(NAALADL2):​c.546-47314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,880 control chromosomes in the GnomAD database, including 11,709 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 0.37 (11709 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.546-47314C>T		intron_variant	Intron 2 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.546-47314C>T		intron_variant	Intron 2 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000485853.5	n.632-47314C>T		intron_variant	Intron 2 of 3	1
NAALADL2	ENST00000473253.5	n.778-47314C>T		intron_variant	Intron 2 of 10	2
NAALADL2	ENST00000489299.5	n.237-31459C>T		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56533 AN: 151760 Hom.: 11700 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.372 AC: 56553 AN: 151880 Hom.: 11709 Cov.: 32 AF XY: 0.371 AC XY: 27520 AN XY: 74252

African (AFR) AF: 0.184 AC: 7632 AN: 41458

American (AMR) AF: 0.396 AC: 6041 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1456 AN: 3460

East Asian (EAS) AF: 0.533 AC: 2747 AN: 5158

South Asian (SAS) AF: 0.412 AC: 1985 AN: 4820

European-Finnish (FIN) AF: 0.362 AC: 3826 AN: 10556

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31311 AN: 67864

Other (OTH) AF: 0.391 AC: 824 AN: 2106

Alfa AF: 0.420 Hom.: 24239

Bravo AF: 0.367

Asia WGS AF: 0.422 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.42
DANN	Benign	0.73
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2861999; hg19: chr3-174904407;