3-175534948-C-T

Variant names:

• chr3-175534948-C-T
• rs78943174
• NM_207015.3:c.1654-41093C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_207015.3(NAALADL2):​c.1654-41093C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 151,660 control chromosomes in the GnomAD database, including 4 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 0.0080 (4 hom., cov: 31)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 14 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.1654-41093C>T		intron_variant	Intron 9 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.1654-41093C>T		intron_variant	Intron 9 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000473253.5	n.1886-41093C>T		intron_variant	Intron 9 of 10	2
NAALADL2	ENST00000489299.5	n.1249-41093C>T		intron_variant	Intron 8 of 10	2

Frequencies

GnomAD3 genomes AF: 0.00798 AC: 1209 AN: 151566 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00264

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.00263

Gnomad ASJ AF: 0.00347

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00417

Gnomad FIN AF: 0.00955

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.00478

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

GnomAD4 genome AF: 0.00797 AC: 1209 AN: 151660 Hom.: 4 Cov.: 31 AF XY: 0.00733 AC XY: 543 AN XY: 74108

African (AFR) AF: 0.00264 AC: 109 AN: 41326

American (AMR) AF: 0.00263 AC: 40 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00347 AC: 12 AN: 3460

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5152

South Asian (SAS) AF: 0.00418 AC: 20 AN: 4790

European-Finnish (FIN) AF: 0.00955 AC: 100 AN: 10472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0132 AC: 899 AN: 67914

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.0122 Hom.: 14

Bravo AF: 0.00743

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.67
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism

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: rs78943174; hg19: chr3-175252736;