NM_207015.3:c.1234+41T>C

Variant names:

• chr3-175447413-T-C
• rs2161041
• NM_207015.3:c.1234+41T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207015.3(NAALADL2):​c.1234+41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000397 in 1,260,312 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207015.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	NM_207015.3	MANE Select	c.1234+41T>C		intron	N/A	NP_996898.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAALADL2	ENST00000454872.6	TSL:1 MANE Select	c.1234+41T>C		intron	N/A	ENSP00000404705.1
	NAALADL2	ENST00000414826.1	TSL:1	n.*99+41T>C		intron	N/A	ENSP00000396969.1
	NAALADL2	ENST00000473253.5	TSL:2	n.1466+41T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000945 AC: 1 AN: 105814 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000397 AC: 5 AN: 1260312 Hom.: 0 Cov.: 17 AF XY: 0.00000321 AC XY: 2 AN XY: 622996

African (AFR) AF: 0.00 AC: 0 AN: 27548

American (AMR) AF: 0.000192 AC: 4 AN: 20850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20340

East Asian (EAS) AF: 0.00 AC: 0 AN: 35114

South Asian (SAS) AF: 0.00 AC: 0 AN: 65612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5222

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 986490

Other (OTH) AF: 0.0000190 AC: 1 AN: 52672

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 18619

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.085
DANN	Benign	0.73
PhyloP100		-1.9

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

Other links and lift over

dbSNP: rs2161041; hg19: chr3-175165201;