Variant 15-75620925-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005701.4(SNUPN):c.127C>T(p.Arg43Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,613,652 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

SNUPN
NM_005701.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

Variant links:

Genes affected

SNUPN (HGNC:14245): (snurportin 1) The nuclear import of the spliceosomal snRNPs U1, U2, U4 and U5, is dependent on the presence of a complex nuclear localization signal. The latter is composed of the 5'-2,2,7-terminal trimethylguanosine (m3G) cap structure of the U snRNA and the Sm core domain. The protein encoded by this gene interacts specifically with m3G-cap and functions as an snRNP-specific nuclear import receptor. Alternatively spliced transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

SNUPN links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07068473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNUPN	NM_005701.4 linkuse as main transcript	c.127C>T	p.Arg43Cys	missense_variant	2/9	ENST00000308588.10	NP_005692.1	O95149
SNUPN	NM_001042581.2 linkuse as main transcript	c.127C>T	p.Arg43Cys	missense_variant	2/9		NP_001036046.1	O95149
SNUPN	NM_001042588.2 linkuse as main transcript	c.127C>T	p.Arg43Cys	missense_variant	2/9		NP_001036053.1	O95149

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNUPN	ENST00000308588.10 linkuse as main transcript	c.127C>T	p.Arg43Cys	missense_variant	2/9	1	NM_005701.4	ENSP00000309831.5		O95149

Frequencies

GnomAD3 genomes

AF:

0.000887

AC:

135

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000817

AC:

205

AN:

250952

Hom.:

AF XY:

0.000825

AC XY:

112

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00162

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.00140

AC:

2045

AN:

1461402

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

997

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000314

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00176

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152250

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.000895

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000774

AC:

EpiCase

AF:

0.00158

EpiControl

AF:

0.000949

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.127C>T (p.R43C) alteration is located in exon 2 (coding exon 1) of the SNUPN gene. This alteration results from a C to T substitution at nucleotide position 127, causing the arginine (R) at amino acid position 43 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;T;T;T;T;.;T;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.96

.;.;.;D;D;D;D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.071

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Uncertain

2.7

M;M;M;M;.;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-6.5

D;D;D;D;D;D;D;D

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;.;D;.;.

Polyphen

1.0

D;D;D;D;.;.;.;.

Vest4

0.83

MVP

0.53

MPC

0.67

ClinPred

0.35

GERP RS

2.7

Varity_R

0.83

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over