rs3914502

Positions:

• chr3-174846812-T-A
• chr3-174846812-T-C
• chr3-174846812-T-G

Variant summary

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

The ENST00000434257.1(NAALADL2):​c.-9+109066T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 151,958 control chromosomes in the GnomAD database, including 38,822 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 0.71 (38822 hom., cov: 30)
• Consequence: NAALADL2 ENST00000434257.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALADL2	XM_006713560.4	c.-9+109066T>A		intron_variant			XP_006713623.1
NAALADL2	XM_017006071.2	c.-9+109066T>A		intron_variant			XP_016861560.1
NAALADL2	XM_017006073.2	c.-9+109066T>A		intron_variant			XP_016861562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000434257.1	c.-9+109066T>A		intron_variant		4		ENSP00000409858.1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107337 AN: 151840 Hom.: 38784 Cov.: 30

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.707 AC: 107437 AN: 151958 Hom.: 38822 Cov.: 30 AF XY: 0.711 AC XY: 52767 AN XY: 74238

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.682

Alfa AF: 0.521 Hom.: 1339

Bravo AF: 0.709

Asia WGS AF: 0.754 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.039
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3914502; hg19: chr3-174564602;