chr3-175178050-C-T

Variant names:

• chr3-175178050-C-T
• rs2035101
• NM_207015.3:c.546-55881C>T

Variant summary

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

The NM_207015.3(NAALADL2):​c.546-55881C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,896 control chromosomes in the GnomAD database, including 8,301 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 0.31 (8301 hom., cov: 31)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.773

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 = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.546-55881C>T		intron_variant	Intron 2 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.546-55881C>T		intron_variant	Intron 2 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000485853.5	n.632-55881C>T		intron_variant	Intron 2 of 3	1
NAALADL2	ENST00000473253.5	n.778-55881C>T		intron_variant	Intron 2 of 10	2
NAALADL2	ENST00000489299.5	n.237-40026C>T		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46785 AN: 151778 Hom.: 8295 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.308 AC: 46800 AN: 151896 Hom.: 8301 Cov.: 31 AF XY: 0.310 AC XY: 22991 AN XY: 74208

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.324

Alfa AF: 0.373 Hom.: 17327

Bravo AF: 0.303

Asia WGS AF: 0.420 AC: 1458 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	1.1
DANN	Benign	0.58

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: rs2035101; hg19: chr3-174895840;