rs7615453

Positions:

• chr3-175192162-T-C
• chr3-175192162-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_207015.3(NAALADL2):​c.546-41769T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,912 control chromosomes in the GnomAD database, including 5,986 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 0.26 (5986 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.546-41769T>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.546-41769T>C		intron_variant		1	NM_207015.3	ENSP00000404705	P1
NAALADL2	ENST00000485853.5	n.632-41769T>C		intron_variant, non_coding_transcript_variant		1
NAALADL2	ENST00000473253.5	n.778-41769T>C		intron_variant, non_coding_transcript_variant		2
NAALADL2	ENST00000489299.5	n.237-25914T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39633 AN: 151794 Hom.: 5984 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.261 AC: 39630 AN: 151912 Hom.: 5986 Cov.: 32 AF XY: 0.261 AC XY: 19410 AN XY: 74228

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.284

Alfa AF: 0.319 Hom.: 10792

Bravo AF: 0.254

Asia WGS AF: 0.305 AC: 1056 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	11
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7615453; hg19: chr3-174909952;