chr3-174990869-T-C

Variant names:

• chr3-174990869-T-C
• rs9813316
• NM_207015.3:c.44-105921T>C

Variant summary

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

The NM_207015.3(NAALADL2):​c.44-105921T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,910 control chromosomes in the GnomAD database, including 12,359 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 0.34 (12359 hom., cov: 31)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207015.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	NM_207015.3	MANE Select	c.44-105921T>C		intron	N/A	NP_996898.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	ENST00000454872.6	TSL:1 MANE Select	c.44-105921T>C		intron	N/A	ENSP00000404705.1
	NAALADL2	ENST00000485853.5	TSL:1	n.130-105921T>C		intron	N/A
	NAALADL2	ENST00000434257.1	TSL:4	c.-8-105921T>C		intron	N/A	ENSP00000409858.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51382 AN: 151792 Hom.: 12319 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.339 AC: 51473 AN: 151910 Hom.: 12359 Cov.: 31 AF XY: 0.335 AC XY: 24855 AN XY: 74274

African (AFR) AF: 0.679 AC: 28112 AN: 41416

American (AMR) AF: 0.275 AC: 4197 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 952 AN: 3464

East Asian (EAS) AF: 0.416 AC: 2140 AN: 5140

South Asian (SAS) AF: 0.299 AC: 1442 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1162 AN: 10586

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.183 AC: 12445 AN: 67926

Other (OTH) AF: 0.332 AC: 699 AN: 2108

Alfa AF: 0.255 Hom.: 14522

Bravo AF: 0.367

Asia WGS AF: 0.368 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		-0.041
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: rs9813316; hg19: chr3-174708659;