chr3-13316486-A-G

Position:

• chr3-13316486-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024923.4(NUP210):​c.*1195T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,192 control chromosomes in the GnomAD database, including 20,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20737 hom., cov: 33)
  • Exomes 𝑓: 0.53 (6 hom.)
• Consequence: NUP210 NM_024923.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.792

Genes affected

NUP210 (HGNC:30052): (nucleoporin 210) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a membrane-spanning glycoprotein that is a major component of the nuclear pore complex. Multiple pseudogenes related to this gene are located on chromosome 3. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-13316486-A-G is Benign according to our data. Variant chr3-13316486-A-G is described in ClinVar as [Benign]. Clinvar id is 1182190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP210	NM_024923.4	c.*1195T>C		3_prime_UTR_variant	40/40	ENST00000254508.7	NP_079199.2
NUP210	XM_047447795.1	c.*1195T>C		3_prime_UTR_variant	22/22		XP_047303751.1
NUP210	XM_047447796.1	c.*1195T>C		3_prime_UTR_variant	22/22		XP_047303752.1
NUP210	XM_047447797.1	c.*1195T>C		3_prime_UTR_variant	22/22		XP_047303753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP210	ENST00000254508.7	c.*1195T>C		3_prime_UTR_variant	40/40	2	NM_024923.4	ENSP00000254508	P1
NUP210	ENST00000695489.1	n.2587T>C		non_coding_transcript_exon_variant	4/4
NUP210	ENST00000695490.1	c.*2287T>C		3_prime_UTR_variant, NMD_transcript_variant	22/22			ENSP00000511960

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79112 AN: 152036 Hom.: 20743 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.526 AC: 20 AN: 38 Hom.: 6 Cov.: 0 AF XY: 0.536 AC XY: 15 AN XY: 28

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.591

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.520 AC: 79154 AN: 152154 Hom.: 20737 Cov.: 33 AF XY: 0.525 AC XY: 39024 AN XY: 74376

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.511

Alfa AF: 0.488 Hom.: 27416

Bravo AF: 0.520

Asia WGS AF: 0.634 AC: 2203 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 29, 2020	This variant is associated with the following publications: (PMID: 22282400) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.63

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: rs354476; hg19: chr3-13357986;