2-108253380-C-T

Variant names:

• chr2-108253380-C-T
• rs746168728
• NM_001320878.2:c.337C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001320878.2(SULT1C3):​c.337C>T​(p.Leu113Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000035 in 1,430,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SULT1C3 NM_001320878.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.892 with no splicing effect.

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.337C>T	p.Leu113Leu	synonymous	Exon 4 of 8	NP_001307807.1	Q6IMI6-2
	SULT1C3	NM_001008743.3		c.337C>T	p.Leu113Leu	synonymous	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.337C>T	p.Leu113Leu	synonymous	Exon 4 of 8	ENSP00000505748.1	Q6IMI6-2
	SULT1C3	ENST00000329106.3	TSL:2	c.337C>T	p.Leu113Leu	synonymous	Exon 4 of 8	ENSP00000333310.2	Q6IMI6-1
	SULT1C3	ENST00000899643.1		c.337C>T	p.Leu113Leu	synonymous	Exon 4 of 9	ENSP00000569702.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000126 AC: 3 AN: 237186 AF XY: 0.00000776

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000336

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000350 AC: 5 AN: 1430030 Hom.: 0 Cov.: 29 AF XY: 0.00000141 AC XY: 1 AN XY: 710860

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

African (AFR) AF: 0.00 AC: 0 AN: 32294

American (AMR) AF: 0.0000251 AC: 1 AN: 39906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39190

South Asian (SAS) AF: 0.00 AC: 0 AN: 80098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1096850

Other (OTH) AF: 0.0000170 AC: 1 AN: 58786

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000315292), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.57
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs746168728; hg19: chr2-108869836;