dbSNP rs966552685: SOWAHC:p.Pro140Thr (chr2-109614907-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_023016.4(SOWAHC):c.418C>A(p.Pro140Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000077 in 1,298,852 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

SOWAHC
NM_023016.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0910

Variant links:

Genes affected

SOWAHC (HGNC:26149): (sosondowah ankyrin repeat domain family member C)

SOWAHC links:

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]

RANBP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060970932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOWAHC	NM_023016.4 link	c.418C>A	p.Pro140Thr	missense_variant	Exon 1 of 1	ENST00000356454.5	NP_075392.2	Q53LP3
RANBP2	XM_047445367.1 link	c.8371-226497C>A		intron_variant	Intron 24 of 24		XP_047301323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOWAHC	ENST00000356454.5 link	c.418C>A	p.Pro140Thr	missense_variant	Exon 1 of 1	6	NM_023016.4	ENSP00000365830.2		Q53LP3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.70e-7

AC:

AN:

1298852

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

634572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.58e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.4

DANN

Benign

0.71

DEOGEN2

Benign

0.0089

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.37

M_CAP

Benign

0.037

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.5

REVEL

Benign

0.032

Sift

Uncertain

0.011

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.049

MutPred

0.17

Loss of catalytic residue at P139 (P = 0.0165);

MVP

0.030

ClinPred

0.056

GERP RS

-0.024

Varity_R

0.11

gMVP

0.26

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over