NM_024923.4:c.*1195T>C

Variant names:

• chr3-13316486-A-G
• rs354476
• NM_024923.4:c.*1195T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

NUP210 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
NUP210	NM_024923.4	c.*1195T>C		3_prime_UTR_variant	Exon 40 of 40	ENST00000254508.7	NP_079199.2
NUP210	XM_047447795.1	c.*1195T>C		3_prime_UTR_variant	Exon 22 of 22		XP_047303751.1
NUP210	XM_047447797.1	c.*1195T>C		3_prime_UTR_variant	Exon 22 of 22		XP_047303753.1
NUP210	XM_047447796.1	c.*1195T>C		3_prime_UTR_variant	Exon 22 of 22		XP_047303752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP210	ENST00000254508.7	c.*1195T>C		3_prime_UTR_variant	Exon 40 of 40	2	NM_024923.4	ENSP00000254508.5
NUP210	ENST00000695489.1	n.2587T>C		non_coding_transcript_exon_variant	Exon 4 of 4
NUP210	ENST00000695490.1	n.*2287T>C		non_coding_transcript_exon_variant	Exon 22 of 22			ENSP00000511960.1
NUP210	ENST00000695490.1	n.*2287T>C		3_prime_UTR_variant	Exon 22 of 22			ENSP00000511960.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 5 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.591 AC: 13 AN: 22

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.510 AC: 21187 AN: 41512

American (AMR) AF: 0.593 AC: 9071 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1626 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3564 AN: 5170

South Asian (SAS) AF: 0.644 AC: 3106 AN: 4820

European-Finnish (FIN) AF: 0.538 AC: 5696 AN: 10594

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33259 AN: 67966

Other (OTH) AF: 0.511 AC: 1081 AN: 2114

Alfa AF: 0.494 Hom.: 45843

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-0.79
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: rs354476; hg19: chr3-13357986;