16-28606829-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001055.4(SULT1A1):c.526G>A(p.Val176Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 151,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 36)
  • Exomes 𝑓: 0.000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SULT1A1 NM_001055.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.69

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.864

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT1A1	NM_001055.4	c.526G>A	p.Val176Met	missense_variant	6/8	ENST00000314752.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT1A1	ENST00000314752.12	c.526G>A	p.Val176Met	missense_variant	6/8	1	NM_001055.4	P1
SULT1A1	ENST00000569554.5	c.526G>A	p.Val176Met	missense_variant	5/7	1		P1
SULT1A1	ENST00000566189.5	c.526G>A	p.Val176Met	missense_variant	6/8	5
SULT1A1	ENST00000567512.1	c.400G>A	p.Val134Met	missense_variant	5/6	3

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151876 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251220 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000205 AC: 30 AN: 1460520 Hom.: 0 Cov.: 89 AF XY: 0.0000193 AC XY: 14 AN XY: 726592

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151876 Hom.: 0 Cov.: 36 AF XY: 0.0000270 AC XY: 2 AN XY: 74174

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

Oct 12, 2022

The c.526G>A (p.V176M) alteration is located in exon 6 (coding exon 5) of the SULT1A1 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the valine (V) at amino acid position 176 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	Uncertain	0.55
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Uncertain	0.040
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.73	D;.;D;D;D;.;D
Eigen	Uncertain	0.41
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.036	D
MutationAssessor	Pathogenic	3.6	H;.;H;H;H;.;.
MutationTaster	Benign	0.98	N;N;N;N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D;D;D
Sift	Uncertain	0.0020	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;T;D;D;D;.;.
Polyphen		0.98	D;D;D;D;D;.;.
Vest4		0.83
MutPred		0.72		Gain of phosphorylation at Y173 (P = 0.1936);.;Gain of phosphorylation at Y173 (P = 0.1936);Gain of phosphorylation at Y173 (P = 0.1936);Gain of phosphorylation at Y173 (P = 0.1936);Gain of phosphorylation at Y173 (P = 0.1936);.;
MVP		0.86
MPC		0.022
ClinPred		0.96	D
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.80
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs771427204; hg19: chr16-28618150;