2-108253356-G-T

Variant names:

• chr2-108253356-G-T
• rs747393318
• NM_001320878.2:c.313G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001320878.2(SULT1C3):​c.313G>T​(p.Val105Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 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. V105I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SULT1C3 NM_001320878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• Publications: 0 publications found

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]

ENSG00000294676 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320878.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1C3	NM_001320878.2	MANE Select	c.313G>T	p.Val105Phe	missense	Exon 4 of 8	NP_001307807.1	Q6IMI6-2
	SULT1C3	NM_001008743.3		c.313G>T	p.Val105Phe	missense	Exon 4 of 8	NP_001008743.1	Q6IMI6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1C3	ENST00000681802.2	MANE Select	c.313G>T	p.Val105Phe	missense	Exon 4 of 8	ENSP00000505748.1	Q6IMI6-2
	SULT1C3	ENST00000329106.3	TSL:2	c.313G>T	p.Val105Phe	missense	Exon 4 of 8	ENSP00000333310.2	Q6IMI6-1
	SULT1C3	ENST00000899643.1		c.313G>T	p.Val105Phe	missense	Exon 4 of 9	ENSP00000569702.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1387044 Hom.: 0 Cov.: 29 AF XY: 0.00000145 AC XY: 1 AN XY: 688502

African (AFR) AF: 0.00 AC: 0 AN: 30600

American (AMR) AF: 0.00 AC: 0 AN: 32720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23092

East Asian (EAS) AF: 0.00 AC: 0 AN: 38484

South Asian (SAS) AF: 0.00 AC: 0 AN: 71832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5424

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077190

Other (OTH) AF: 0.00 AC: 0 AN: 56780

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.73	N
PhyloP100		2.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.086
Sift	Uncertain	0.016	D
Sift4G	Benign	0.11	T
Polyphen		0.56	P
Vest4		0.19
MutPred		0.53		Loss of sheet (P = 0.0483)
MVP		0.15
MPC		0.21
ClinPred		0.31	T
GERP RS		3.0
Varity_R		0.19
gMVP		0.41
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.24		Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747393318; hg19: chr2-108869812;