16-28607061-C-A

Variant names:

• chr16-28607061-C-A
• NM_001055.4:c.389G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PP3_Strong

The NM_001055.4(SULT1A1):​c.389G>T​(p.Arg130Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SULT1A1 NM_001055.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.53

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]

ENSG00000289755 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity ST1A1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1A1	NM_001055.4	c.389G>T	p.Arg130Leu	missense_variant	Exon 5 of 8	ENST00000314752.12	NP_001046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1A1	ENST00000314752.12	c.389G>T	p.Arg130Leu	missense_variant	Exon 5 of 8	1	NM_001055.4	ENSP00000321988.7

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460450 Hom.: 0 Cov.: 54 AF XY: 0.00000275 AC XY: 2 AN XY: 726552

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.91	D;.;D;D;D;.;D
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.077
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.99	.;D;D;.;.;D;D
M_CAP	Benign	0.0088	T
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	4.0	H;.;H;H;H;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.7	D;D;D;D;D;D;D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;.;.
Polyphen		1.0	D;D;D;D;D;.;.
Vest4		0.84
MutPred		0.95		Loss of MoRF binding (P = 0.0323);.;Loss of MoRF binding (P = 0.0323);Loss of MoRF binding (P = 0.0323);Loss of MoRF binding (P = 0.0323);Loss of MoRF binding (P = 0.0323);.;
MVP		0.71
MPC		0.070
ClinPred		1.0	D
GERP RS		1.4
Varity_R		0.84
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr16-28618382;