1-185174947-G-A

Position:

• chr1-185174947-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000367500.9(SWT1):​c.800G>A​(p.Arg267Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SWT1 ENST00000367500.9 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0460

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040088803).
• BP6: Variant 1-185174947-G-A is Benign according to our data. Variant chr1-185174947-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2483540.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SWT1	NM_017673.7	c.800G>A	p.Arg267Lys	missense_variant	5/19	ENST00000367500.9	NP_060143.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SWT1	ENST00000367500.9	c.800G>A	p.Arg267Lys	missense_variant	5/19	1	NM_017673.7	ENSP00000356470	P1
SWT1	ENST00000367501.7	c.800G>A	p.Arg267Lys	missense_variant	5/19	2		ENSP00000356471	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.45
DEOGEN2	Benign	0.000031	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.76	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.14	N;N
REVEL	Benign	0.021
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.021
MutPred		0.18		Gain of ubiquitination at R267 (P = 0.0011);Gain of ubiquitination at R267 (P = 0.0011);
MVP		0.014
MPC		0.14
ClinPred		0.042	T
GERP RS		-3.8
Varity_R		0.035
gMVP		0.10

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: rs1248994260; hg19: chr1-185144079;