NM_207015.3:c.819+9394T>C

Variant names:

• chr3-175243598-T-C
• rs1463525
• NM_207015.3:c.819+9394T>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.819+9394T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 141,552 control chromosomes in the GnomAD database, including 9,918 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 (9918 hom., cov: 21)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 15 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]

NAALADL2-AS2 (HGNC:41015): (NAALADL2 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.819+9394T>C		intron_variant	Intron 3 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.819+9394T>C		intron_variant	Intron 3 of 13	1	NM_207015.3	ENSP00000404705.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 52123 AN: 141458 Hom.: 9902 Cov.: 21

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.369 AC: 52172 AN: 141552 Hom.: 9918 Cov.: 21 AF XY: 0.367 AC XY: 24963 AN XY: 68032

African (AFR) AF: 0.355 AC: 13467 AN: 37910

American (AMR) AF: 0.255 AC: 3431 AN: 13432

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1448 AN: 3406

East Asian (EAS) AF: 0.358 AC: 1670 AN: 4664

South Asian (SAS) AF: 0.434 AC: 1899 AN: 4376

European-Finnish (FIN) AF: 0.390 AC: 3212 AN: 8246

Middle Eastern (MID) AF: 0.378 AC: 102 AN: 270

European-Non Finnish (NFE) AF: 0.388 AC: 25761 AN: 66408

Other (OTH) AF: 0.348 AC: 678 AN: 1946

Alfa AF: 0.382 Hom.: 35522

Bravo AF: 0.360

Asia WGS AF: 0.372 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.39
PhyloP100		-0.076
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: rs1463525; hg19: chr3-174961387;