1-185160858-C-G

Position:

• chr1-185160858-C-G

Variant summary

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

The NM_017673.7(SWT1):​c.17C>G​(p.Ser6Cys) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SWT1 NM_017673.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

Genes affected

SWT1 (HGNC:16785): (SWT1 RNA endoribonuclease homolog) Predicted to be active in nucleus. [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=0.13596377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SWT1	NM_017673.7	c.17C>G	p.Ser6Cys	missense_variant	2/19	ENST00000367500.9	NP_060143.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SWT1	ENST00000367500.9	c.17C>G	p.Ser6Cys	missense_variant	2/19	1	NM_017673.7	ENSP00000356470	P1
SWT1	ENST00000367501.7	c.17C>G	p.Ser6Cys	missense_variant	2/19	2		ENSP00000356471	P1
SWT1	ENST00000450350.1	c.17C>G	p.Ser6Cys	missense_variant	2/5	2		ENSP00000401413

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

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

Oct 16, 2023

The c.17C>G (p.S6C) alteration is located in exon 2 (coding exon 1) of the SWT1 gene. This alteration results from a C to G substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 to be replaced by a cysteine (C). 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	0.085
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0026	T;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.72	.;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.6	L;L;.
MutationTaster	Benign	0.72	D;D
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N;N;D
REVEL	Benign	0.061
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.96	D;D;.
Vest4		0.38
MutPred		0.21		Loss of phosphorylation at S6 (P = 0.0028);Loss of phosphorylation at S6 (P = 0.0028);Loss of phosphorylation at S6 (P = 0.0028);
MVP		0.31
MPC		0.46
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.15
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1447327492; hg19: chr1-185129990;