rs11075253

chr16-15054789-C-Achr16-15054789-C-T

Variant summary

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

The NM_173474.4(NTAN1):c.81+1102G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,134 control chromosomes in the GnomAD database, including 4,406 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 0.22 (4406 hom., cov: 32)
• Consequence: NTAN1 NM_173474.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTAN1	NM_173474.4	c.81+1102G>T		intron_variant		ENST00000287706.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTAN1	ENST00000287706.8	c.81+1102G>T		intron_variant		1	NM_173474.4	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33546 AN: 152014 Hom.: 4411 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.220 AC: 33530 AN: 152134 Hom.: 4406 Cov.: 32 AF XY: 0.217 AC XY: 16170 AN XY: 74364

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.253

Alfa AF: 0.279 Hom.: 6918

Bravo AF: 0.211

Asia WGS AF: 0.0770 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.3
Dann	Benign	0.80

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: rs11075253; hg19: chr16-15148646;