16-28592403-C-T

Variant names:

• chr16-28592403-C-T
• NM_001054.4:c.635G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001054.4(SULT1A2):​c.635G>A​(p.Gly212Glu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SULT1A2 NM_001054.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1A2	NM_001054.4	c.635G>A	p.Gly212Glu	missense_variant	Exon 7 of 8	ENST00000335715.9	NP_001045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1A2	ENST00000335715.9	c.635G>A	p.Gly212Glu	missense_variant	Exon 7 of 8	1	NM_001054.4	ENSP00000338742.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.635G>A (p.G212E) alteration is located in exon 7 (coding exon 6) of the SULT1A2 gene. This alteration results from a G to A substitution at nucleotide position 635, causing the glycine (G) at amino acid position 212 to be replaced by a glutamic acid (E). 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	0.23
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Uncertain	0.53	D;T;T
Eigen	Benign	-0.030
Eigen_PC	Benign	0.064
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.76	T;.;T
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.7	.;L;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.41
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.64	T;T;T
Polyphen		0.60	.;P;P
Vest4		0.47
MutPred		0.72		.;Gain of disorder (P = 0.0212);Gain of disorder (P = 0.0212);
MVP		0.95
MPC		0.16
ClinPred		0.52	D
GERP RS		3.0
Varity_R		0.34
gMVP		0.52

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-28603724;