3-175359897-T-C

Variant names:

• chr3-175359897-T-C
• rs4894485
• NM_207015.3:c.1090+35572T>C

Variant summary

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

The NM_207015.3(NAALADL2):​c.1090+35572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 151,984 control chromosomes in the GnomAD database, including 30,812 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 0.63 (30812 hom., cov: 32)
• Consequence: NAALADL2 NM_207015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAALADL2	NM_207015.3	c.1090+35572T>C		intron_variant	Intron 5 of 13	ENST00000454872.6	NP_996898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAALADL2	ENST00000454872.6	c.1090+35572T>C		intron_variant	Intron 5 of 13	1	NM_207015.3	ENSP00000404705.1
NAALADL2	ENST00000414826.1	n.121-87332T>C		intron_variant	Intron 1 of 6	1		ENSP00000396969.1
NAALADL2	ENST00000473253.5	n.1322+35572T>C		intron_variant	Intron 5 of 10	2
NAALADL2	ENST00000489299.5	n.829+35572T>C		intron_variant	Intron 5 of 10	2

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96414 AN: 151866 Hom.: 30778 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.635 AC: 96506 AN: 151984 Hom.: 30812 Cov.: 32 AF XY: 0.634 AC XY: 47088 AN XY: 74286

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.621

Alfa AF: 0.601 Hom.: 53639

Bravo AF: 0.642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.7
DANN	Benign	0.61

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: rs4894485; hg19: chr3-175077686;