rs16966953

Variant names:

• chr16-15041997-A-G
• rs16966953
• NM_173474.4:c.434-321T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173474.4(NTAN1):​c.434-321T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,082 control chromosomes in the GnomAD database, including 7,419 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 (7419 hom., cov: 32)
• Consequence: NTAN1 NM_173474.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173474.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTAN1	NM_173474.4	MANE Select	c.434-321T>C		intron	N/A	NP_775745.1
	PDXDC1	NM_001285449.2		c.1399+11941A>G		intron	N/A	NP_001272378.1
	PDXDC1	NM_001324020.2		c.1396+11941A>G		intron	N/A	NP_001310949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTAN1	ENST00000287706.8	TSL:1 MANE Select	c.434-321T>C		intron	N/A	ENSP00000287706.3
	PDXDC1	ENST00000535621.6	TSL:1	c.1399+11941A>G		intron	N/A	ENSP00000437835.2
	PDXDC1	ENST00000850604.1		c.1399+11941A>G		intron	N/A	ENSP00000520891.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45796 AN: 151964 Hom.: 7397 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.302 AC: 45867 AN: 152082 Hom.: 7419 Cov.: 32 AF XY: 0.308 AC XY: 22868 AN XY: 74364

African (AFR) AF: 0.215 AC: 8934 AN: 41488

American (AMR) AF: 0.440 AC: 6730 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1108 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1914 AN: 5166

South Asian (SAS) AF: 0.404 AC: 1942 AN: 4810

European-Finnish (FIN) AF: 0.340 AC: 3600 AN: 10584

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20669 AN: 67960

Other (OTH) AF: 0.319 AC: 673 AN: 2110

Alfa AF: 0.271 Hom.: 1459

Bravo AF: 0.308

Asia WGS AF: 0.418 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.75
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16966953; hg19: chr16-15135854;