dbSNP rs145344319: SULT1C3:p.Ile4Thr (chr2-108247205-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001320878.2(SULT1C3):c.11T>C(p.Ile4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,522,032 control chromosomes in the GnomAD database, including 4 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 3 hom. )

Consequence

SULT1C3
NM_001320878.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.421

Variant links:

Genes affected

SULT1C3 (HGNC:33543): (sulfotransferase family 1C member 3) Enables 3'-phosphoadenosine 5'-phosphosulfate binding activity and sulfotransferase activity. Involved in 3'-phosphoadenosine 5'-phosphosulfate metabolic process; cholesterol metabolic process; and xenobiotic metabolic process. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SULT1C3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070406795).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1C3	NM_001320878.2 link	c.11T>C	p.Ile4Thr	missense_variant	Exon 2 of 8	ENST00000681802.2	NP_001307807.1	Q6IMI6-2
SULT1C3	NM_001008743.3 link	c.11T>C	p.Ile4Thr	missense_variant	Exon 2 of 8		NP_001008743.1	Q6IMI6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1C3	ENST00000681802.2 link	c.11T>C	p.Ile4Thr	missense_variant	Exon 2 of 8		NM_001320878.2	ENSP00000505748.1		Q6IMI6-2
SULT1C3	ENST00000329106.3 link	c.11T>C	p.Ile4Thr	missense_variant	Exon 2 of 8	2		ENSP00000333310.2		Q6IMI6-1

Frequencies

GnomAD3 genomes

AF:

0.00122

AC:

185

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00132

AC:

278

AN:

210834

Hom.:

AF XY:

0.00145

AC XY:

166

AN XY:

114794

show subpopulations

Gnomad AFR exome

AF:

0.0000690

Gnomad AMR exome

AF:

0.000900

Gnomad ASJ exome

AF:

0.00413

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00170

Gnomad OTH exome

AF:

0.00123

GnomAD4 exome

AF:

0.00176

AC:

2416

AN:

1369834

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1229

AN XY:

675140

show subpopulations

Gnomad4 AFR exome

AF:

0.000333

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00225

Gnomad4 EAS exome

AF:

0.0000533

Gnomad4 SAS exome

AF:

0.00205

Gnomad4 FIN exome

AF:

0.0000786

Gnomad4 NFE exome

AF:

0.00188

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

AF:

0.00122

AC:

185

AN:

152198

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00215

Hom.:

Bravo

AF:

0.00125

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00137

AC:

166

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.11T>C (p.I4T) alteration is located in exon 1 (coding exon 1) of the SULT1C3 gene. This alteration results from a T to C substitution at nucleotide position 11, causing the isoleucine (I) at amino acid position 4 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

0.061

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.037

DANN

Benign

0.50

DEOGEN2

Benign

0.0015

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.33

M_CAP

Benign

0.0015

MetaRNN

Benign

0.0070

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.40

REVEL

Benign

0.023

Sift

Benign

0.25

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.037

MVP

0.15

MPC

0.071

ClinPred

0.0040

GERP RS

-5.4

Varity_R

0.031

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over