3-175447413-T-G

Position:

• chr3-175447413-T-G

Variant summary

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

The NM_207015.3(NAALADL2):​c.1234+41T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,409,842 control chromosomes in the GnomAD database, including 478,711 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 0.80 (49396 hom., cov: 32)
  • Exomes 𝑓: 0.83 (429315 hom.)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAALADL2	NM_207015.3	c.1234+41T>G		intron_variant		ENST00000454872.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAALADL2	ENST00000454872.6	c.1234+41T>G		intron_variant		1	NM_207015.3	P1
NAALADL2	ENST00000414826.1	c.*99+41T>G		intron_variant, NMD_transcript_variant		1
NAALADL2	ENST00000473253.5	n.1466+41T>G		intron_variant, non_coding_transcript_variant		2
NAALADL2	ENST00000489299.5	n.830-15988T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122190 AN: 152012 Hom.: 49369 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.868

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.836

GnomAD3 exomes AF: 0.842 AC: 89140 AN: 105814 Hom.: 37664 AF XY: 0.846 AC XY: 46532 AN XY: 54996

Gnomad AFR exome AF: 0.720

Gnomad AMR exome AF: 0.866

Gnomad ASJ exome AF: 0.882

Gnomad EAS exome AF: 0.966

Gnomad SAS exome AF: 0.854

Gnomad FIN exome AF: 0.838

Gnomad NFE exome AF: 0.828

Gnomad OTH exome AF: 0.846

GnomAD4 exome AF: 0.825 AC: 1037980 AN: 1257710 Hom.: 429315 Cov.: 17 AF XY: 0.827 AC XY: 514321 AN XY: 621792

Gnomad4 AFR exome AF: 0.711

Gnomad4 AMR exome AF: 0.860

Gnomad4 ASJ exome AF: 0.882

Gnomad4 EAS exome AF: 0.948

Gnomad4 SAS exome AF: 0.849

Gnomad4 FIN exome AF: 0.835

Gnomad4 NFE exome AF: 0.819

Gnomad4 OTH exome AF: 0.831

GnomAD4 genome AF: 0.804 AC: 122269 AN: 152132 Hom.: 49396 Cov.: 32 AF XY: 0.808 AC XY: 60044 AN XY: 74352

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.838

Alfa AF: 0.790 Hom.: 7454

Bravo AF: 0.802

Asia WGS AF: 0.894 AC: 3107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.078
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2161041; hg19: chr3-175165201;