1-185174418-T-A

Position:

• chr1-185174418-T-A

Variant summary

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

The NM_017673.7(SWT1):​c.271T>A​(p.Ser91Thr) 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. 14/21 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: 2.72

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=0.13816544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SWT1	NM_017673.7	c.271T>A	p.Ser91Thr	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.271T>A	p.Ser91Thr	missense_variant	5/19	1	NM_017673.7	ENSP00000356470	P1
SWT1	ENST00000367501.7	c.271T>A	p.Ser91Thr	missense_variant	5/19	2		ENSP00000356471	P1
SWT1	ENST00000450350.1	c.271T>A	p.Ser91Thr	missense_variant	5/5	2		ENSP00000401413

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000893 AC: 2 AN: 223918 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 121530

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000118

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

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

Nov 21, 2023

The c.271T>A (p.S91T) alteration is located in exon 5 (coding exon 4) of the SWT1 gene. This alteration results from a T to A substitution at nucleotide position 271, causing the serine (S) at amino acid position 91 to be replaced by a threonine (T). 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	0.082
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.020	T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.66	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.97	N;N;D
REVEL	Benign	0.051
Sift	Uncertain	0.027	D;D;D
Sift4G	Benign	0.080	T;T;T
Polyphen		0.67	P;P;.
Vest4		0.22
MutPred		0.31		Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);
MVP		0.20
MPC		0.25
ClinPred		0.30	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs745323310; hg19: chr1-185143550;