3-175506108-G-A

Position:

• chr3-175506108-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_207015.3(NAALADL2):​c.1653+34350G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 152,068 control chromosomes in the GnomAD database, including 54 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 0.024 (54 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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=-0.75).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0235 (3579/152068) while in subpopulation NFE AF= 0.0348 (2366/67990). AF 95% confidence interval is 0.0336. There are 54 homozygotes in gnomad4. There are 1649 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 54 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.1653+34350G>A		intron_variant		ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.1653+34350G>A		intron_variant		1	NM_207015.3	ENSP00000404705	P1
NAALADL2	ENST00000473253.5	n.1885+34350G>A		intron_variant, non_coding_transcript_variant		2
NAALADL2	ENST00000489299.5	n.1248+34350G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3580 AN: 151950 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.00682

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.0240

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

GnomAD4 genome AF: 0.0235 AC: 3579 AN: 152068 Hom.: 54 Cov.: 32 AF XY: 0.0222 AC XY: 1649 AN XY: 74338

Gnomad4 AFR AF: 0.00677

Gnomad4 AMR AF: 0.0335

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0195 Hom.: 8

Bravo AF: 0.0237

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.4
DANN	Benign	0.66

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: rs74619861; hg19: chr3-175223896;