3-175359897-T-C

Variant names:

• chr3-175359897-T-C
• rs4894485
• NM_207015.3:c.1090+35572T>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.1090+35572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 151,984 control chromosomes in the GnomAD database, including 30,812 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 0.63 (30812 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 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.1090+35572T>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.1090+35572T>C		intron	N/A	ENSP00000404705.1
	NAALADL2	ENST00000414826.1	TSL:1	n.121-87332T>C		intron	N/A	ENSP00000396969.1
	NAALADL2	ENST00000473253.5	TSL:2	n.1322+35572T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96414 AN: 151866 Hom.: 30778 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.635 AC: 96506 AN: 151984 Hom.: 30812 Cov.: 32 AF XY: 0.634 AC XY: 47088 AN XY: 74286

African (AFR) AF: 0.678 AC: 28137 AN: 41494

American (AMR) AF: 0.646 AC: 9831 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3470

East Asian (EAS) AF: 0.675 AC: 3485 AN: 5160

South Asian (SAS) AF: 0.514 AC: 2479 AN: 4826

European-Finnish (FIN) AF: 0.701 AC: 7415 AN: 10576

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.611 AC: 41524 AN: 67916

Other (OTH) AF: 0.621 AC: 1310 AN: 2110

Alfa AF: 0.609 Hom.: 82301

Bravo AF: 0.642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.7
DANN	Benign	0.61
PhyloP100		-0.55
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: rs4894485; hg19: chr3-175077686;