16-28605867-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001055.4(SULT1A1):c.842C>T(p.Ala281Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000856 in 151,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A281T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000056 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: SULT1A1 NM_001055.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0870

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13223872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT1A1	NM_001055.4	c.842C>T	p.Ala281Val	missense_variant	8/8	ENST00000314752.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT1A1	ENST00000314752.12	c.842C>T	p.Ala281Val	missense_variant	8/8	1	NM_001055.4	P1
SULT1A1	ENST00000569554.5	c.842C>T	p.Ala281Val	missense_variant	7/7	1		P1
SULT1A1	ENST00000566189.5	c.842C>T	p.Ala281Val	missense_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.0000857 AC: 13 AN: 151726 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000482

GnomAD3 exomes AF: 0.0000564 AC: 14 AN: 248440 Hom.: 0 AF XY: 0.0000595 AC XY: 8 AN XY: 134400

Gnomad AFR exome AF: 0.000437

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000658

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000447

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000556 AC: 81 AN: 1457670 Hom.: 2 Cov.: 36 AF XY: 0.0000538 AC XY: 39 AN XY: 725104

Gnomad4 AFR exome AF: 0.000509

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000581

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000477

Gnomad4 OTH exome AF: 0.0000831

GnomAD4 genome AF: 0.0000856 AC: 13 AN: 151844 Hom.: 0 Cov.: 34 AF XY: 0.000121 AC XY: 9 AN XY: 74220

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000477

Alfa AF: 0.000422 Hom.: 0

ExAC AF: 0.0000907 AC: 11

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

Dec 18, 2023

The c.842C>T (p.A281V) alteration is located in exon 8 (coding exon 7) of the SULT1A1 gene. This alteration results from a C to T substitution at nucleotide position 842, causing the alanine (A) at amino acid position 281 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.28
Cadd	Benign	12
Dann	Benign	0.97
DEOGEN2	Uncertain	0.49	T;.;T;T;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.080	N
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.089	T;T;T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.5	M;.;M;M;M;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N
Sift	Benign	0.061	T;T;T;T;T;T
Sift4G	Uncertain	0.049	D;T;D;D;D;.
Polyphen		0.0060	B;B;B;B;B;.
Vest4		0.059
MVP		0.84
MPC		1.5
ClinPred		0.043	T
GERP RS		0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.43

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: rs569953298; hg19: chr16-28617188; COSMIC: COSV59089904; COSMIC: COSV59089904;