3-175357320-G-T

Variant names:

• chr3-175357320-G-T
• rs6771725
• NM_207015.3:c.1090+32995G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207015.3(NAALADL2):​c.1090+32995G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,934 control chromosomes in the GnomAD database, including 6,348 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 0.28 (6348 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.1090+32995G>T		intron_variant	Intron 5 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.1090+32995G>T		intron_variant	Intron 5 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000414826.1	n.121-89909G>T		intron_variant	Intron 1 of 6	1		ENSP00000396969.1
NAALADL2	ENST00000473253.5	n.1322+32995G>T		intron_variant	Intron 5 of 10	2
NAALADL2	ENST00000489299.5	n.829+32995G>T		intron_variant	Intron 5 of 10	2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42858 AN: 151816 Hom.: 6349 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.282 AC: 42873 AN: 151934 Hom.: 6348 Cov.: 32 AF XY: 0.287 AC XY: 21300 AN XY: 74232

African (AFR) AF: 0.223 AC: 9258 AN: 41462

American (AMR) AF: 0.320 AC: 4872 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 942 AN: 3466

East Asian (EAS) AF: 0.496 AC: 2558 AN: 5162

South Asian (SAS) AF: 0.238 AC: 1147 AN: 4810

European-Finnish (FIN) AF: 0.381 AC: 4004 AN: 10522

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19177 AN: 67954

Other (OTH) AF: 0.283 AC: 597 AN: 2110

Alfa AF: 0.278 Hom.: 24943

Bravo AF: 0.280

Asia WGS AF: 0.364 AC: 1265 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.4
DANN	Benign	0.61
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6771725; hg19: chr3-175075109;