rs6791089

Positions:

• chr3-175797635-A-C
• chr3-175797635-A-T

Variant summary

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

The NM_207015.3(NAALADL2):​c.2190-5370A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,006 control chromosomes in the GnomAD database, including 1,784 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 0.13 (1784 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.2190-5370A>C		intron_variant		ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.2190-5370A>C		intron_variant		1	NM_207015.3	ENSP00000404705	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20139 AN: 151888 Hom.: 1760 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0871

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.133 AC: 20221 AN: 152006 Hom.: 1784 Cov.: 32 AF XY: 0.137 AC XY: 10151 AN XY: 74270

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.0871

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0634

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0698 Hom.: 662

Bravo AF: 0.145

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.50

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: rs6791089; hg19: chr3-175515423;