NM_001379267.1:c.90-366C>G

Variant names:

• chr9-128276221-C-G
• rs762033604
• NM_001379267.1:c.90-366C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001379267.1(SWI5):​c.90-366C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,611,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SWI5 NM_001379267.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.54
• Publications: 1 publications found

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]

GOLGA2 Gene-Disease associations (from GenCC):

• developmental delay with hypotonia, myopathy, and brain abnormalities

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04541409).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379267.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SWI5	NM_001379267.1		c.90-366C>G		intron	N/A	NP_001366196.1
	SWI5	NM_001318092.2		c.90-486C>G		intron	N/A	NP_001305021.1	H7C5E9
	GOLGA2	NM_001366244.2	MANE Select	c.-245G>C		upstream_gene	N/A	NP_001353173.2	A0A8J9BZL8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SWI5	ENST00000372898.6	TSL:5	c.57-486C>G		intron	N/A	ENSP00000361989.2	H3BLW9
	SWI5	ENST00000495313.5	TSL:3	c.90-486C>G		intron	N/A	ENSP00000419719.2	H7C5E9
	GOLGA2	ENST00000611957.5	TSL:1 MANE Select	c.-245G>C		upstream_gene	N/A	ENSP00000478799.2	A0A8J9BZL8

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151812 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1459266 Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12 AN XY: 725644

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1110638

Other (OTH) AF: 0.0000166 AC: 1 AN: 60250

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151812 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74156

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41350

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5100

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67898

Other (OTH) AF: 0.00 AC: 0 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.13
DANN	Benign	0.45
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.0010
Sift	Benign	0.090	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.13
MVP		0.092
MPC		0.20
ClinPred		0.13	T
GERP RS		-5.4
PromoterAI		-0.20	Neutral
Varity_R		0.051
gMVP		0.031

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

Other links and lift over

dbSNP: rs762033604; hg19: chr9-131038500; COSMIC: COSV60792083; COSMIC: COSV60792083;