chr2-108247302-G-A

Variant names:

• chr2-108247302-G-A
• rs112050262
• NM_001320878.2:c.108G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001320878.2(SULT1C3):​c.108G>A​(p.Trp36*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0187 in 1,598,718 control chromosomes in the GnomAD database, including 452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.016 (22 hom., cov: 32)
  • Exomes 𝑓: 0.019 (430 hom.)
• Consequence: SULT1C3 NM_001320878.2 stop_gained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.18
• Publications: 13 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 2-108247302-G-A is Benign according to our data. Variant chr2-108247302-G-A is described in ClinVar as Benign. ClinVar VariationId is 403503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

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.108G>A	p.Trp36*	stop_gained	Exon 2 of 8	NP_001307807.1	Q6IMI6-2
	SULT1C3	NM_001008743.3		c.108G>A	p.Trp36*	stop_gained	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.108G>A	p.Trp36*	stop_gained	Exon 2 of 8	ENSP00000505748.1	Q6IMI6-2
	SULT1C3	ENST00000329106.3	TSL:2	c.108G>A	p.Trp36*	stop_gained	Exon 2 of 8	ENSP00000333310.2	Q6IMI6-1
	SULT1C3	ENST00000899643.1		c.108G>A	p.Trp36*	stop_gained	Exon 2 of 9	ENSP00000569702.1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2420 AN: 152108 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.0216 AC: 5278 AN: 244308 AF XY: 0.0237

Gnomad AFR exome AF: 0.0109

Gnomad AMR exome AF: 0.00910

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00429

Gnomad FIN exome AF: 0.0346

Gnomad NFE exome AF: 0.0185

Gnomad OTH exome AF: 0.0179

GnomAD4 exome AF: 0.0190 AC: 27510 AN: 1446492 Hom.: 430 Cov.: 33 AF XY: 0.0203 AC XY: 14569 AN XY: 718922

African (AFR) AF: 0.00934 AC: 308 AN: 32962

American (AMR) AF: 0.00995 AC: 433 AN: 43500

Ashkenazi Jewish (ASJ) AF: 0.00990 AC: 255 AN: 25768

East Asian (EAS) AF: 0.00390 AC: 153 AN: 39256

South Asian (SAS) AF: 0.0560 AC: 4655 AN: 83136

European-Finnish (FIN) AF: 0.0328 AC: 1734 AN: 52922

Middle Eastern (MID) AF: 0.0187 AC: 107 AN: 5724

European-Non Finnish (NFE) AF: 0.0171 AC: 18836 AN: 1103550

Other (OTH) AF: 0.0172 AC: 1029 AN: 59674

GnomAD4 genome AF: 0.0159 AC: 2428 AN: 152226 Hom.: 22 Cov.: 32 AF XY: 0.0173 AC XY: 1288 AN XY: 74434

African (AFR) AF: 0.0103 AC: 430 AN: 41552

American (AMR) AF: 0.0119 AC: 182 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3468

East Asian (EAS) AF: 0.00540 AC: 28 AN: 5184

South Asian (SAS) AF: 0.0469 AC: 226 AN: 4818

European-Finnish (FIN) AF: 0.0315 AC: 334 AN: 10600

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0167 AC: 1133 AN: 68006

Other (OTH) AF: 0.0194 AC: 41 AN: 2112

Alfa AF: 0.0168 Hom.: 87

Bravo AF: 0.0138

TwinsUK AF: 0.0175 AC: 65

ALSPAC AF: 0.0179 AC: 69

ESP6500AA AF: 0.0120 AC: 53

ESP6500EA AF: 0.0171 AC: 147

ExAC AF: 0.0241 AC: 2931

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Uncertain	0.45
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.60	D
PhyloP100		4.2
Vest4		0.082
GERP RS		4.0
Mutation Taster		=18/182	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.38		Position offset: -4

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

Other links and lift over

dbSNP: rs112050262; hg19: chr2-108863758; COSMIC: COSV61253396;