9-128276736-G-T

Variant names:

• chr9-128276736-G-T
• NM_001318089.2:c.92G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318089.2(SWI5):​c.92G>T​(p.Arg31Leu) variant causes a missense 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. 13/20 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: 31)
• Consequence: SWI5 NM_001318089.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.715

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]

ACMG classification

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=0.13136426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SWI5	NM_001318089.2	c.92G>T	p.Arg31Leu	missense_variant	Exon 2 of 5	ENST00000418976.3	NP_001305018.2
SWI5	NM_001379267.1	c.239G>T	p.Arg80Leu	missense_variant	Exon 2 of 5		NP_001366196.1
SWI5	NM_001040011.2	c.212G>T	p.Arg71Leu	missense_variant	Exon 2 of 5		NP_001035100.2
SWI5	NM_001318092.2	c.119G>T	p.Arg40Leu	missense_variant	Exon 2 of 5		NP_001305021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SWI5	ENST00000418976.3	c.92G>T	p.Arg31Leu	missense_variant	Exon 2 of 5	2	NM_001318089.2	ENSP00000411469.3

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

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.407G>T (p.R136L) alteration is located in exon 2 (coding exon 2) of the SWI5 gene. This alteration results from a G to T substitution at nucleotide position 407, causing the arginine (R) at amino acid position 136 to be replaced by a leucine (L). 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	0.29
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T;T;T;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.75	T;T;T;T;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;L;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.8	N;D;.;.;.
REVEL	Benign	0.034
Sift	Benign	0.18	T;T;.;.;.
Sift4G	Benign	0.18	T;D;T;T;T
Polyphen		0.92	.;P;.;.;.
Vest4		0.30
MutPred		0.24		.;Loss of MoRF binding (P = 0.012);.;.;.;
MVP		0.22
MPC		0.69
ClinPred		0.78	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.10
gMVP		0.14

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: chr9-131039015;