chr16-28593344-A-G

Position:

• chr16-28593344-A-G

Variant summary

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

The NM_001054.4(SULT1A2):​c.502T>C​(p.Ser168Pro) variant causes a missense, splice region 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. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SULT1A2 NM_001054.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.683

Genes affected

SULT1A2 (HGNC:11454): (sulfotransferase family 1A member 2) Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene encodes one of two phenol sulfotransferases with thermostable enzyme activity. Two alternatively spliced variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

ENSG00000288656 (HGNC:):

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=0.34207025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT1A2	NM_001054.4	c.502T>C	p.Ser168Pro	missense_variant, splice_region_variant	6/8	ENST00000335715.9	NP_001045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT1A2	ENST00000335715.9	c.502T>C	p.Ser168Pro	missense_variant, splice_region_variant	6/8	1	NM_001054.4	ENSP00000338742.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2023

The c.502T>C (p.S168P) alteration is located in exon 6 (coding exon 5) of the SULT1A2 gene. This alteration results from a T to C substitution at nucleotide position 502, causing the serine (S) at amino acid position 168 to be replaced by a proline (P). 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	0.13
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.19	T;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.60	.;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.36	T;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.89	P;P;.
Vest4		0.35
MutPred		0.59		Loss of catalytic residue at S168 (P = 0.0432);Loss of catalytic residue at S168 (P = 0.0432);Loss of catalytic residue at S168 (P = 0.0432);
MVP		0.70
MPC		0.40
ClinPred		0.46	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.85
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs891602583; hg19: chr16-28604665; COSMIC: COSV100187259; COSMIC: COSV100187259;