16-28606849-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001055.4(SULT1A1):c.506A>T(p.Tyr169Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y169C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 36)
• Consequence: SULT1A1 NM_001055.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.423

Genes affected

SULT1A1 (HGNC:11453): (sulfotransferase family 1A member 1) 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. Multiple alternatively spliced variants that encode two isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT1A1	NM_001055.4	c.506A>T	p.Tyr169Phe	missense_variant	6/8	ENST00000314752.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT1A1	ENST00000314752.12	c.506A>T	p.Tyr169Phe	missense_variant	6/8	1	NM_001055.4	P1
SULT1A1	ENST00000569554.5	c.506A>T	p.Tyr169Phe	missense_variant	5/7	1		P1
SULT1A1	ENST00000566189.5	c.506A>T	p.Tyr169Phe	missense_variant	6/8	5
SULT1A1	ENST00000567512.1	c.380A>T	p.Tyr127Phe	missense_variant	5/6	3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 90

GnomAD4 genome Cov.: 36

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

Sep 27, 2022

The c.506A>T (p.Y169F) alteration is located in exon 6 (coding exon 5) of the SULT1A1 gene. This alteration results from a A to T substitution at nucleotide position 506, causing the tyrosine (Y) at amino acid position 169 to be replaced by a phenylalanine (F). 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	0.17
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	15
Dann	Benign	0.90
DEOGEN2	Uncertain	0.48	T;.;T;T;T;.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.21	N
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.7	L;.;L;L;L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N;N
Sift	Benign	0.41	T;T;T;T;T;T;T
Sift4G	Benign	0.67	T;T;T;T;T;.;.
Polyphen		0.080	B;P;B;B;B;.;.
Vest4		0.38
MutPred		0.79		Loss of phosphorylation at Y169 (P = 0.1525);.;Loss of phosphorylation at Y169 (P = 0.1525);Loss of phosphorylation at Y169 (P = 0.1525);Loss of phosphorylation at Y169 (P = 0.1525);Loss of phosphorylation at Y169 (P = 0.1525);.;
MVP		0.78
MPC		0.015
ClinPred		0.49	T
GERP RS		1.3
Varity_R		0.62
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-28618170;