NM_207015.3:c.1090+22695G>A

Variant names:

• chr3-175347020-G-A
• rs10936845
• NM_207015.3:c.1090+22695G>A

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+22695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,148 control chromosomes in the GnomAD database, including 2,441 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 0.14 (2441 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.1090+22695G>A		intron_variant	Intron 5 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.1090+22695G>A		intron_variant	Intron 5 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000414826.1	n.120+90490G>A		intron_variant	Intron 1 of 6	1		ENSP00000396969.1
NAALADL2	ENST00000473253.5	n.1322+22695G>A		intron_variant	Intron 5 of 10	2
NAALADL2	ENST00000489299.5	n.829+22695G>A		intron_variant	Intron 5 of 10	2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21984 AN: 152030 Hom.: 2420 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.145 AC: 22038 AN: 152148 Hom.: 2441 Cov.: 32 AF XY: 0.143 AC XY: 10641 AN XY: 74386

African (AFR) AF: 0.313 AC: 12994 AN: 41484

American (AMR) AF: 0.0865 AC: 1322 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 331 AN: 3472

East Asian (EAS) AF: 0.0551 AC: 285 AN: 5168

South Asian (SAS) AF: 0.0738 AC: 356 AN: 4826

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10584

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.0752 AC: 5111 AN: 68010

Other (OTH) AF: 0.143 AC: 302 AN: 2108

Alfa AF: 0.0975 Hom.: 1527

Bravo AF: 0.151

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.72
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: rs10936845; hg19: chr3-175064809;