NM_001379267.1:c.90-429G>C

Variant summary

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

The NM_001379267.1(SWI5):​c.90-429G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SWI5
NM_001379267.1 intron

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0230
Variant links:
Genes affected
SWI5 (HGNC:31412): (SWI5 homologous recombination repair protein) Involved in cellular response to ionizing radiation and double-strand break repair via homologous recombination. Part of Swi5-Sfr1 complex. [provided by Alliance of Genome Resources, Apr 2022]
GOLGA2 (HGNC:4425): (golgin A2) The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked cisternae (flattened membrane sacs). Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. This gene encodes one of the golgins, a family of proteins localized to the Golgi. This encoded protein has been postulated to play roles in the stacking of Golgi cisternae and in vesicular transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of these variants has not been determined. [provided by RefSeq, Feb 2010]

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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=0.05927524).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GOLGA2NM_001366244.2 linkc.-182C>G upstream_gene_variant ENST00000611957.5 NP_001353173.2
SWI5NM_001318089.2 linkc.-183G>C upstream_gene_variant ENST00000418976.3 NP_001305018.2 Q1ZZU3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GOLGA2ENST00000611957.5 linkc.-182C>G upstream_gene_variant 1 NM_001366244.2 ENSP00000478799.2 A0A8J9BZL8
SWI5ENST00000418976.3 linkc.-183G>C upstream_gene_variant 2 NM_001318089.2 ENSP00000411469.3 H7C3F2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.13G>C (p.G5R) alteration is located in exon 1 (coding exon 1) of the SWI5 gene. This alteration results from a G to C substitution at nucleotide position 13, causing the glycine (G) at amino acid position 5 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
Uncertain
0.38
BayesDel_addAF
Benign
-0.025
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
3.5
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0034
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.57
N
REVEL
Benign
0.15
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.0010
B
Vest4
0.17
MutPred
0.22
Gain of helix (P = 0.0143);
MVP
0.12
MPC
0.69
ClinPred
0.43
T
GERP RS
-2.3
Varity_R
0.15
gMVP
0.0080

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.

Other links and lift over

hg19: chr9-131038437; API