NM_001320878.2:c.5C>T

Variant names:

• chr2-108247199-C-T
• rs758796049
• NM_001320878.2:c.5C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001320878.2(SULT1C3):​c.5C>T​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,513,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: SULT1C3 NM_001320878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.681
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10099468).

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.5C>T	p.Ala2Val	missense	Exon 2 of 8	NP_001307807.1	Q6IMI6-2
	SULT1C3	NM_001008743.3		c.5C>T	p.Ala2Val	missense	Exon 2 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.5C>T	p.Ala2Val	missense	Exon 2 of 8	ENSP00000505748.1	Q6IMI6-2
	SULT1C3	ENST00000329106.3	TSL:2	c.5C>T	p.Ala2Val	missense	Exon 2 of 8	ENSP00000333310.2	Q6IMI6-1
	SULT1C3	ENST00000899643.1		c.5C>T	p.Ala2Val	missense	Exon 2 of 9	ENSP00000569702.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151900 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000624 AC: 13 AN: 208378 AF XY: 0.0000705

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000263

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000208

GnomAD4 exome AF: 0.0000286 AC: 39 AN: 1361318 Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 24 AN XY: 670528

African (AFR) AF: 0.0000336 AC: 1 AN: 29748

American (AMR) AF: 0.000246 AC: 8 AN: 32570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22796

East Asian (EAS) AF: 0.000188 AC: 7 AN: 37258

South Asian (SAS) AF: 0.0000734 AC: 5 AN: 68104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5384

European-Non Finnish (NFE) AF: 0.0000123 AC: 13 AN: 1059164

Other (OTH) AF: 0.0000899 AC: 5 AN: 55630

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151900 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74180

African (AFR) AF: 0.0000484 AC: 2 AN: 41340

American (AMR) AF: 0.0000656 AC: 1 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000577 AC: 7

ClinVar

ClinVar submissions

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	0.17
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.68
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.062
Sift	Benign	0.21	T
Sift4G	Benign	0.23	T
Polyphen		0.94	P
Vest4		0.24
MutPred		0.27		Gain of methylation at K3 (P = 0.0315)
MVP		0.14
MPC		0.37
ClinPred		0.043	T
GERP RS		0.80
Varity_R		0.039
gMVP		0.58
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs758796049; hg19: chr2-108863655; COSMIC: COSV61253680;