rs7651836

Variant names:

• chr3-175143894-T-C
• rs7651836
• NM_207015.3:c.545+46603T>C

Variant summary

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

The NM_207015.3(NAALADL2):​c.545+46603T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,624 control chromosomes in the GnomAD database, including 6,603 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 0.29 (6603 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.545+46603T>C		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.545+46603T>C		intron_variant	Intron 2 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000485853.5	n.631+46603T>C		intron_variant	Intron 2 of 3	1
NAALADL2	ENST00000473253.5	n.777+46603T>C		intron_variant	Intron 2 of 10	2
NAALADL2	ENST00000489299.5	n.236+19253T>C		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44372 AN: 151506 Hom.: 6590 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.293 AC: 44419 AN: 151624 Hom.: 6603 Cov.: 32 AF XY: 0.291 AC XY: 21587 AN XY: 74104

African (AFR) AF: 0.343 AC: 14214 AN: 41388

American (AMR) AF: 0.287 AC: 4357 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1082 AN: 3460

East Asian (EAS) AF: 0.202 AC: 1045 AN: 5172

South Asian (SAS) AF: 0.338 AC: 1631 AN: 4820

European-Finnish (FIN) AF: 0.255 AC: 2686 AN: 10544

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18431 AN: 67736

Other (OTH) AF: 0.322 AC: 676 AN: 2100

Alfa AF: 0.283 Hom.: 27022

Bravo AF: 0.298

Asia WGS AF: 0.333 AC: 1154 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.84
PhyloP100		-1.0
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: rs7651836; hg19: chr3-174861684;