chr2-108253356-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001320878.2(SULT1C3):​c.313G>A​(p.Val105Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,539,058 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SULT1C3 NM_001320878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089107215).

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>A	p.Val105Ile	missense	Exon 4 of 8	NP_001307807.1	Q6IMI6-2
	SULT1C3	NM_001008743.3		c.313G>A	p.Val105Ile	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>A	p.Val105Ile	missense	Exon 4 of 8	ENSP00000505748.1	Q6IMI6-2
	SULT1C3	ENST00000329106.3	TSL:2	c.313G>A	p.Val105Ile	missense	Exon 4 of 8	ENSP00000333310.2	Q6IMI6-1
	SULT1C3	ENST00000899643.1		c.313G>A	p.Val105Ile	missense	Exon 4 of 9	ENSP00000569702.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152016 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000933 AC: 2 AN: 214326 AF XY: 0.00000855

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000975

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000180 AC: 25 AN: 1387042 Hom.: 0 Cov.: 29 AF XY: 0.0000189 AC XY: 13 AN XY: 688500

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

American (AMR) AF: 0.0000306 AC: 1 AN: 32720

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

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38484

South Asian (SAS) AF: 0.0000278 AC: 2 AN: 71832

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 50922

Middle Eastern (MID) AF: 0.000184 AC: 1 AN: 5424

European-Non Finnish (NFE) AF: 0.0000130 AC: 14 AN: 1077190

Other (OTH) AF: 0.0000881 AC: 5 AN: 56778

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152016 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74236

African (AFR) AF: 0.0000241 AC: 1 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.9
DANN	Benign	0.96
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.58	N
PhyloP100		2.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.082
Sift	Benign	0.071	T
Sift4G	Benign	0.21	T
Polyphen		0.016	B
Vest4		0.12
MVP		0.081
MPC		0.065
ClinPred		0.13	T
GERP RS		3.0
Varity_R		0.095
gMVP		0.14
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs747393318; hg19: chr2-108869812;