2-109614860-C-G

Variant summary

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

The NM_023016.4(SOWAHC):​c.371C>G​(p.Pro124Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000314 in 1,399,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

SOWAHC
NM_023016.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0350
Variant links:
Genes affected
SOWAHC (HGNC:26149): (sosondowah ankyrin repeat domain family member C)
RANBP2 (HGNC:9848): (RAN binding protein 2) RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.12774223).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SOWAHCNM_023016.4 linkc.371C>G p.Pro124Arg missense_variant Exon 1 of 1 ENST00000356454.5 NP_075392.2 Q53LP3
RANBP2XM_047445367.1 linkc.8371-226544C>G intron_variant Intron 24 of 24 XP_047301323.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SOWAHCENST00000356454.5 linkc.371C>G p.Pro124Arg missense_variant Exon 1 of 1 6 NM_023016.4 ENSP00000365830.2 Q53LP3

Frequencies

GnomAD3 genomes
AF:
0.0000856
AC:
13
AN:
151932
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000736
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000666
AC:
1
AN:
15006
Hom.:
0
AF XY:
0.000112
AC XY:
1
AN XY:
8922
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000167
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000248
AC:
31
AN:
1247608
Hom.:
0
Cov.:
35
AF XY:
0.0000180
AC XY:
11
AN XY:
609634
show subpopulations
Gnomad4 AFR exome
AF:
0.0000823
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000245
Gnomad4 OTH exome
AF:
0.0000777
GnomAD4 genome
AF:
0.0000856
AC:
13
AN:
151932
Hom.:
0
Cov.:
33
AF XY:
0.0000270
AC XY:
2
AN XY:
74198
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.000106

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 01, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.371C>G (p.P124R) alteration is located in exon 1 (coding exon 1) of the SOWAHC gene. This alteration results from a C to G substitution at nucleotide position 371, causing the proline (P) at amino acid position 124 to be replaced by an arginine (R). 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
0.076
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
12
DANN
Benign
0.74
DEOGEN2
Benign
0.0099
T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.26
T
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.024
Sift
Benign
0.41
T
Sift4G
Benign
0.18
T
Polyphen
0.99
D
Vest4
0.037
MVP
0.12
ClinPred
0.039
T
GERP RS
2.8
Varity_R
0.048
gMVP
0.23

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

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

Other links and lift over

dbSNP: rs931502294; hg19: chr2-110372437; API