2-108247199-C-G

Variant names:

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

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.5C>G​(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. A2V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SULT1C3 NM_001320878.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.13822252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1C3	NM_001320878.2	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 8	ENST00000681802.2	NP_001307807.1
SULT1C3	NM_001008743.3	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 8		NP_001008743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1C3	ENST00000681802.2	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 8		NM_001320878.2	ENSP00000505748.1
SULT1C3	ENST00000329106.3	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 8	2		ENSP00000333310.2
ENSG00000294676	ENST00000725207.1	n.168-11336G>C		intron_variant	Intron 1 of 1
ENSG00000294676	ENST00000725208.1	n.43-11336G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.68
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.030
Sift	Benign	0.16	T
Sift4G	Benign	0.19	T
Polyphen		0.79	P
Vest4		0.19
MutPred		0.21		Loss of stability (P = 0.0353);
MVP		0.095
MPC		0.37
ClinPred		0.13	T
GERP RS		0.80
Varity_R		0.059
gMVP		0.45
Mutation Taster		=98/2	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;