chr15-75607263-C-T

Variant summary

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

The NM_005701.4(SNUPN):​c.553G>A​(p.Val185Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,613,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SNUPN
NM_005701.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83
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]

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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=0.122193605).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNUPNNM_005701.4 linkuse as main transcriptc.553G>A p.Val185Ile missense_variant 6/9 ENST00000308588.10 NP_005692.1 O95149
SNUPNNM_001042581.2 linkuse as main transcriptc.553G>A p.Val185Ile missense_variant 6/9 NP_001036046.1 O95149
SNUPNNM_001042588.2 linkuse as main transcriptc.553G>A p.Val185Ile missense_variant 6/9 NP_001036053.1 O95149

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNUPNENST00000308588.10 linkuse as main transcriptc.553G>A p.Val185Ile missense_variant 6/91 NM_005701.4 ENSP00000309831.5 O95149

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000155
AC:
39
AN:
251184
Hom.:
0
AF XY:
0.000184
AC XY:
25
AN XY:
135746
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.000256
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000157
AC:
230
AN:
1461574
Hom.:
0
Cov.:
30
AF XY:
0.000150
AC XY:
109
AN XY:
727090
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.000184
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000209
Hom.:
0
Bravo
AF:
0.000162
ESP6500AA
AF:
0.000228
AC:
1
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000132
AC:
16
EpiCase
AF:
0.000327
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsJul 14, 2024The c.553G>A (p.V185I) alteration is located in exon 6 (coding exon 5) of the SNUPN gene. This alteration results from a G to A substitution at nucleotide position 553, causing the valine (V) at amino acid position 185 to be replaced by an isoleucine (I). 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
Benign
0.070
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
14
DANN
Benign
0.95
DEOGEN2
Benign
0.044
T;T;T;T;.;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.060
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.80
.;.;.;T;T;T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.12
T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.56
N;N;N;N;.;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.22
N;N;N;N;N;N
REVEL
Benign
0.053
Sift
Benign
0.42
T;T;T;T;T;T
Sift4G
Benign
0.74
T;T;T;T;T;.
Polyphen
0.0020
B;B;B;B;.;.
Vest4
0.32
MVP
0.25
MPC
0.10
ClinPred
0.11
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.044
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs148518590; hg19: chr15-75899604; API