Genetic Variant SULT1C3:p.Ala2Glu (chr2-108247199-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001320878.2(SULT1C3):c.5C>A(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,361,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SULT1C3
NM_001320878.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.681

Publications

0 publications found

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:

ENSG00000294676 (HGNC:):

ENSG00000294676 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11881399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1C3	NM_001320878.2 link	c.5C>A	p.Ala2Glu	missense_variant	Exon 2 of 8	ENST00000681802.2	NP_001307807.1	Q6IMI6-2
SULT1C3	NM_001008743.3 link	c.5C>A	p.Ala2Glu	missense_variant	Exon 2 of 8		NP_001008743.1	Q6IMI6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SULT1C3	ENST00000681802.2 link	c.5C>A	p.Ala2Glu	missense_variant	Exon 2 of 8		NM_001320878.2	ENSP00000505748.1	Q6IMI6-2
SULT1C3	ENST00000329106.3 link	c.5C>A	p.Ala2Glu	missense_variant	Exon 2 of 8	2		ENSP00000333310.2	Q6IMI6-1
ENSG00000294676	ENST00000725207.1 link	n.168-11336G>T		intron_variant	Intron 1 of 1
ENSG00000294676	ENST00000725208.1 link	n.43-11336G>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.35e-7

AC:

AN:

1361314

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

670526

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29748

American (AMR)

AF:

0.00

AC:

AN:

32570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22796

East Asian (EAS)

AF:

0.00

AC:

AN:

37258

South Asian (SAS)

AF:

0.00

AC:

AN:

68104

European-Finnish (FIN)

AF:

0.0000197

AC:

AN:

50664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5384

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1059160

Other (OTH)

AF:

0.00

AC:

AN:

55630

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.9

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.23

M_CAP

Benign

0.0018

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

PhyloP100

0.68

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.28

REVEL

Benign

0.034

Sift

Benign

0.042

Sift4G

Uncertain

0.057

Polyphen

0.049

Vest4

0.28

MutPred

0.27

Loss of ubiquitination at K3 (P = 0.0352);

MVP

0.10

MPC

0.39

ClinPred

0.30

GERP RS

0.80

Varity_R

0.076

gMVP

0.65

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over