3-175534948-C-T

Position:

• chr3-175534948-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NAALADL2	NM_207015.3	c.1654-41093C>T		intron_variant		ENST00000454872.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAALADL2	ENST00000454872.6	c.1654-41093C>T		intron_variant		1	NM_207015.3	P1
NAALADL2	ENST00000473253.5	n.1886-41093C>T		intron_variant, non_coding_transcript_variant		2
NAALADL2	ENST00000489299.5	n.1249-41093C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.00264

Gnomad4 AMR AF: 0.00263

Gnomad4 ASJ AF: 0.00347

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00418

Gnomad4 FIN AF: 0.00955

Gnomad4 NFE AF: 0.0132

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00823 Hom.: 2

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs78943174; hg19: chr3-175252736;