NM_001320878.2:c.20A>C

Variant names:

• chr2-108247214-A-C
• NM_001320878.2:c.20A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001320878.2(SULT1C3):​c.20A>C​(p.Asn7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,376,574 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: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SULT1C3 NM_001320878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.360
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062038332).

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.20A>C	p.Asn7Thr	missense	Exon 2 of 8	NP_001307807.1	Q6IMI6-2
	SULT1C3	NM_001008743.3		c.20A>C	p.Asn7Thr	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.20A>C	p.Asn7Thr	missense	Exon 2 of 8	ENSP00000505748.1	Q6IMI6-2
	SULT1C3	ENST00000329106.3	TSL:2	c.20A>C	p.Asn7Thr	missense	Exon 2 of 8	ENSP00000333310.2	Q6IMI6-1
	SULT1C3	ENST00000899643.1		c.20A>C	p.Asn7Thr	missense	Exon 2 of 9	ENSP00000569702.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1376574 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 678938

African (AFR) AF: 0.00 AC: 0 AN: 30434

American (AMR) AF: 0.00 AC: 0 AN: 34506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23494

East Asian (EAS) AF: 0.00 AC: 0 AN: 37614

South Asian (SAS) AF: 0.00 AC: 0 AN: 70732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5444

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1066848

Other (OTH) AF: 0.00 AC: 0 AN: 56378

GnomAD4 genome Cov.: 32

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	0.072
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.7
DANN	Benign	0.93
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.36
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.0090
Sift	Uncertain	0.027	D
Sift4G	Benign	0.40	T
Polyphen		0.028	B
Vest4		0.18
MutPred		0.24		Loss of catalytic residue at N7 (P = 0.0699)
MVP		0.16
MPC		0.12
ClinPred		0.072	T
GERP RS		1.8
Varity_R		0.091
gMVP		0.27
Mutation Taster		=100/0	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

hg19: chr2-108863670;