rs6788338

Positions:

• chr3-175337708-C-G
• chr3-175337708-C-T

Variant summary

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

The NM_207015.3(NAALADL2):​c.1090+13383C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,936 control chromosomes in the GnomAD database, including 11,464 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 0.38 (11464 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAALADL2	NM_207015.3	c.1090+13383C>G		intron_variant		ENST00000454872.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAALADL2	ENST00000454872.6	c.1090+13383C>G		intron_variant		1	NM_207015.3	P1
NAALADL2	ENST00000414826.1	c.120+81178C>G		intron_variant, NMD_transcript_variant		1
NAALADL2	ENST00000473253.5	n.1322+13383C>G		intron_variant, non_coding_transcript_variant		2
NAALADL2	ENST00000489299.5	n.829+13383C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58142 AN: 151816 Hom.: 11458 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.383 AC: 58176 AN: 151936 Hom.: 11464 Cov.: 32 AF XY: 0.382 AC XY: 28348 AN XY: 74254

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.389

Alfa AF: 0.409 Hom.: 1605

Bravo AF: 0.367

Asia WGS AF: 0.362 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.020
DANN	Benign	0.36

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: rs6788338; hg19: chr3-175055497;