3-174867918-C-G

Position:

• chr3-174867918-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207015.3(NAALADL2):​c.43+8468C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,808 control chromosomes in the GnomAD database, including 3,623 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 0.19 (3623 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.43+8468C>G		intron_variant		ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.43+8468C>G		intron_variant		1	NM_207015.3	ENSP00000404705	P1
NAALADL2	ENST00000485853.5	n.129+8468C>G		intron_variant, non_coding_transcript_variant		1
NAALADL2	ENST00000434257.1	c.-9+130172C>G		intron_variant		4		ENSP00000409858
NAALADL2	ENST00000473253.5	n.275+3828C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28493 AN: 151694 Hom.: 3607 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.188 AC: 28545 AN: 151808 Hom.: 3623 Cov.: 32 AF XY: 0.187 AC XY: 13861 AN XY: 74168

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0405

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.175

Alfa AF: 0.0645 Hom.: 74

Bravo AF: 0.189

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.93
DANN	Benign	0.32

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: rs10513725; hg19: chr3-174585708;