9-128284620-G-C

Position:

• chr9-128284620-G-C

Variant summary

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

The NM_001318089.2(SWI5):​c.222G>C​(p.Gln74His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: SWI5 NM_001318089.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.24

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=0.18303263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SWI5	NM_001318089.2	c.222G>C	p.Gln74His	missense_variant	3/5	ENST00000418976.3	NP_001305018.2
SWI5	NM_001379267.1	c.369G>C	p.Gln123His	missense_variant	3/5		NP_001366196.1
SWI5	NM_001040011.2	c.342G>C	p.Gln114His	missense_variant	3/5		NP_001035100.2
SWI5	NM_001318092.2	c.249G>C	p.Gln83His	missense_variant	3/5		NP_001305021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SWI5	ENST00000418976.3	c.222G>C	p.Gln74His	missense_variant	3/5	2	NM_001318089.2	ENSP00000411469.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 22, 2023

The c.537G>C (p.Q179H) alteration is located in exon 3 (coding exon 3) of the SWI5 gene. This alteration results from a G to C substitution at nucleotide position 537, causing the glutamine (Q) at amino acid position 179 to be replaced by a histidine (H). 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	0.35
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;T;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.65	T;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	.;M;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.5	.;D;.;.;.
REVEL	Benign	0.23
Sift	Uncertain	0.0030	.;D;.;.;.
Sift4G	Uncertain	0.026	D;D;D;D;D
Polyphen		1.0	.;D;.;.;.
Vest4		0.46
MutPred		0.55		.;Gain of catalytic residue at I177 (P = 0.1118);.;.;.;
MVP		0.030
MPC		0.63
ClinPred		0.99	D
GERP RS		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.50
gMVP		0.22

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

Other links and lift over

dbSNP: rs1213638571; hg19: chr9-131046899;