rs10513728

Positions:

• chr3-174963270-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207015.3(NAALADL2):​c.43+103820A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 152,270 control chromosomes in the GnomAD database, including 124 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 0.026 (124 hom., cov: 33)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAALADL2	NM_207015.3	c.43+103820A>G		intron_variant		ENST00000454872.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAALADL2	ENST00000454872.6	c.43+103820A>G		intron_variant		1	NM_207015.3	P1
NAALADL2	ENST00000485853.5	n.129+103820A>G		intron_variant, non_coding_transcript_variant		1
NAALADL2	ENST00000434257.1	c.-8-133520A>G		intron_variant		4
NAALADL2	ENST00000473253.5	n.275+99180A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4024 AN: 152152 Hom.: 124 Cov.: 33

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00852

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00939

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0265 AC: 4029 AN: 152270 Hom.: 124 Cov.: 33 AF XY: 0.0257 AC XY: 1914 AN XY: 74442

Gnomad4 AFR AF: 0.0712

Gnomad4 AMR AF: 0.00851

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0414

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00939

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0249 Hom.: 16

Bravo AF: 0.0286

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs10513728; hg19: chr3-174681060;