2-108253380-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001320878.2(SULT1C3):​c.337C>A​(p.Leu113Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 7.0e-7 (0 hom.)
• Consequence: SULT1C3 NM_001320878.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.892

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28167862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1C3	NM_001320878.2	c.337C>A	p.Leu113Met	missense_variant	Exon 4 of 8	ENST00000681802.2	NP_001307807.1
SULT1C3	NM_001008743.3	c.337C>A	p.Leu113Met	missense_variant	Exon 4 of 8		NP_001008743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1C3	ENST00000681802.2	c.337C>A	p.Leu113Met	missense_variant	Exon 4 of 8		NM_001320878.2	ENSP00000505748.1
SULT1C3	ENST00000329106.3	c.337C>A	p.Leu113Met	missense_variant	Exon 4 of 8	2		ENSP00000333310.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430030 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 710860

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.337C>A (p.L113M) alteration is located in exon 3 (coding exon 3) of the SULT1C3 gene. This alteration results from a C to A substitution at nucleotide position 337, causing the leucine (L) at amino acid position 113 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.2
DANN	Benign	0.92
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.063
Sift	Benign	0.064	T
Sift4G	Uncertain	0.053	T
Polyphen		0.025	B
Vest4		0.16
MutPred		0.69		Gain of disorder (P = 0.0785);
MVP		0.067
MPC		0.066
ClinPred		0.16	T
GERP RS		0.095
Varity_R		0.14
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-108869836;