NM_207015.3:c.1801-658C>T

Variant names:

• chr3-175626633-C-T
• rs4129157
• NM_207015.3:c.1801-658C>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.1801-658C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 151,584 control chromosomes in the GnomAD database, including 42,147 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 0.74 (42147 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.1801-658C>T		intron_variant	Intron 10 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.1801-658C>T		intron_variant	Intron 10 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000489299.5	n.1396-658C>T		intron_variant	Intron 9 of 10	2

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112032 AN: 151466 Hom.: 42136 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.660

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.739 AC: 112091 AN: 151584 Hom.: 42147 Cov.: 32 AF XY: 0.742 AC XY: 55008 AN XY: 74098

African (AFR) AF: 0.586 AC: 24233 AN: 41356

American (AMR) AF: 0.815 AC: 12386 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2667 AN: 3456

East Asian (EAS) AF: 0.876 AC: 4520 AN: 5158

South Asian (SAS) AF: 0.815 AC: 3927 AN: 4820

European-Finnish (FIN) AF: 0.800 AC: 8455 AN: 10566

Middle Eastern (MID) AF: 0.662 AC: 192 AN: 290

European-Non Finnish (NFE) AF: 0.787 AC: 53297 AN: 67718

Other (OTH) AF: 0.748 AC: 1574 AN: 2104

Alfa AF: 0.745 Hom.: 5522

Bravo AF: 0.735

Asia WGS AF: 0.802 AC: 2789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.43
DANN	Benign	0.58
PhyloP100		-0.72
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: rs4129157; hg19: chr3-175344421;