rs10936797

Variant names:

• chr3-174476453-T-G
• rs10936797
• ENST00000482228.5:n.113+37768T>G

Variant summary

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

The ENST00000434257.1(NAALADL2):​c.-184+35421T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,758 control chromosomes in the GnomAD database, including 5,949 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 0.27 (5949 hom., cov: 32)
• Consequence: NAALADL2 ENST00000434257.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	XM_006713560.4	c.-184+35421T>G		intron_variant	Intron 1 of 15		XP_006713623.1
NAALADL2	XM_017006075.3	c.-247+35421T>G		intron_variant	Intron 1 of 16		XP_016861564.1
NAALADL2	XM_017006077.3	c.-451+35421T>G		intron_variant	Intron 1 of 18		XP_016861566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000482228.5	n.113+37768T>G		intron_variant	Intron 1 of 1	1
NAALADL2	ENST00000489729.5	n.46+35421T>G		intron_variant	Intron 1 of 3	1
NAALADL2	ENST00000491329.5	n.114-37056T>G		intron_variant	Intron 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40807 AN: 151640 Hom.: 5946 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.269 AC: 40826 AN: 151758 Hom.: 5949 Cov.: 32 AF XY: 0.276 AC XY: 20476 AN XY: 74150

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.282

Alfa AF: 0.284 Hom.: 5761

Bravo AF: 0.257

Asia WGS AF: 0.411 AC: 1419 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10936797; hg19: chr3-174194243;