ENST00000463048.3:n.273G>C

Variant names:

• chr6-149749393-C-G
• rs11155676
• ENST00000463048.3:n.273G>C

Variant summary

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

The ENST00000463048.3(NUP43):​n.273G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 295,990 control chromosomes in the GnomAD database, including 28,157 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 0.43 (15266 hom., cov: 29)
  • Exomes 𝑓: 0.40 (12891 hom.)
• Consequence: NUP43 ENST00000463048.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 8 publications found

Genes affected

NUP43 (HGNC:21182): (nucleoporin 43) Bidirectional transport of macromolecules between the cytoplasm and nucleus occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope. NPCs are composed of subcomplexes, and NUP43 is part of one such subcomplex, Nup107-160 (Loiodice et al., 2004 [PubMed 15146057]).[supplied by OMIM, Mar 2008]

PCMT1 (HGNC:8728): (protein-L-isoaspartate (D-aspartate) O-methyltransferase) This gene encodes a member of the type II class of protein carboxyl methyltransferase enzymes. The encoded enzyme plays a role in protein repair by recognizing and converting D-aspartyl and L-isoaspartyl residues resulting from spontaneous deamidation back to the normal L-aspartyl form. The encoded protein may play a protective role in the pathogenesis of Alzheimer's disease, and single nucleotide polymorphisms in this gene have been associated with spina bifida and premature ovarian failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000463048.3. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP43	ENST00000463048.3	TSL:3	n.273G>C		non_coding_transcript_exon	Exon 1 of 3
	PCMT1	ENST00000367378.6	TSL:1	c.-509C>G		upstream_gene	N/A	ENSP00000356348.2
	PCMT1	ENST00000484601.6	TSL:5	n.-509C>G		upstream_gene	N/A	ENSP00000417448.2

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65666 AN: 151428 Hom.: 15239 Cov.: 29

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.402 AC: 58093 AN: 144448 Hom.: 12891 Cov.: 2 AF XY: 0.401 AC XY: 29171 AN XY: 72756

African (AFR) AF: 0.486 AC: 2108 AN: 4334

American (AMR) AF: 0.608 AC: 2377 AN: 3908

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 2143 AN: 5336

East Asian (EAS) AF: 0.741 AC: 8578 AN: 11578

South Asian (SAS) AF: 0.390 AC: 980 AN: 2516

European-Finnish (FIN) AF: 0.372 AC: 4575 AN: 12294

Middle Eastern (MID) AF: 0.369 AC: 272 AN: 738

European-Non Finnish (NFE) AF: 0.350 AC: 32864 AN: 93768

Other (OTH) AF: 0.421 AC: 4196 AN: 9976

GnomAD4 genome AF: 0.434 AC: 65741 AN: 151542 Hom.: 15266 Cov.: 29 AF XY: 0.439 AC XY: 32534 AN XY: 74034

African (AFR) AF: 0.492 AC: 20293 AN: 41242

American (AMR) AF: 0.560 AC: 8511 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1404 AN: 3460

East Asian (EAS) AF: 0.811 AC: 4183 AN: 5156

South Asian (SAS) AF: 0.410 AC: 1967 AN: 4798

European-Finnish (FIN) AF: 0.378 AC: 3973 AN: 10514

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.354 AC: 24034 AN: 67874

Other (OTH) AF: 0.445 AC: 935 AN: 2102

Alfa AF: 0.395 Hom.: 1314

Bravo AF: 0.458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.75
PhyloP100		1.6
PromoterAI		-0.13	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11155676; hg19: chr6-150070529;