rs4500751

Variant names:

• chr16-15046354-C-T
• rs4500751
• NM_173474.4:c.359+1088G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 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
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• 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 rank	MANE	Protein	UniProt
NTAN1	NM_173474.4	c.359+1088G>A		intron_variant	Intron 4 of 9	ENST00000287706.8	NP_775745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTAN1	ENST00000287706.8	c.359+1088G>A		intron_variant	Intron 4 of 9	1	NM_173474.4	ENSP00000287706.3

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

African (AFR) AF: 0.208 AC: 8637 AN: 41468

American (AMR) AF: 0.451 AC: 6893 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1245 AN: 3462

East Asian (EAS) AF: 0.327 AC: 1689 AN: 5168

South Asian (SAS) AF: 0.405 AC: 1954 AN: 4824

European-Finnish (FIN) AF: 0.332 AC: 3499 AN: 10552

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21200 AN: 67948

Other (OTH) AF: 0.325 AC: 688 AN: 2114

Alfa AF: 0.314 Hom.: 32308

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
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4500751; hg19: chr16-15140211;