rs4500751

chr16-15046354-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_173474.4(NTAN1):c.359+1088G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,016 control chromosomes in the GnomAD database, including 7,492 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 0.30 (7492 hom., cov: 31)
• Consequence: NTAN1 NM_173474.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62

Genes affected

NTAN1 (HGNC:29909): (N-terminal asparagine amidase) The protein encoded by this gene functions in a step-wise process of protein degradation through the N-end rule pathway. This protein acts as a tertiary destabilizing enzyme that deamidates N-terminal L-Asn residues on proteins to produce N-terminal L-Asp. L-Asp substrates are subsequently conjugated to L-Arg, which is recognized by specific E3 ubiquitin ligases and targeted to the proteasome. Pseudogenes of this gene are located on the long arms of chromosomes 8, 10 and 12. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

PDXDC1 (HGNC:28995): (pyridoxal dependent decarboxylase domain containing 1) Enables cadherin binding activity. Predicted to be involved in carboxylic acid metabolic process. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTAN1	NM_173474.4	c.359+1088G>A		intron_variant		ENST00000287706.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTAN1	ENST00000287706.8	c.359+1088G>A		intron_variant		1	NM_173474.4	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46077 AN: 151900 Hom.: 7471 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.304 AC: 46140 AN: 152016 Hom.: 7492 Cov.: 31 AF XY: 0.309 AC XY: 22952 AN XY: 74316

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.325

Alfa AF: 0.317 Hom.: 14711

Bravo AF: 0.310

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	15
Dann	Benign	0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.58		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.58		Position offset: 3

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

Publications

LitVar

Other links and lift over

dbSNP: rs4500751; hg19: chr16-15140211;