rs777884064

Variant names:

• chr16-28608331-A-C
• rs777884064
• NM_001055.4:c.332T>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001055.4(SULT1A1):​c.332T>G​(p.Leu111Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,612,230 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000059 (3 hom.)
• Consequence: SULT1A1 NM_001055.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37935185).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001055.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A1	NM_001055.4	MANE Select	c.332T>G	p.Leu111Arg	missense	Exon 4 of 8	NP_001046.2
	SULT1A1	NM_001394421.1		c.332T>G	p.Leu111Arg	missense	Exon 7 of 11	NP_001381350.1	P50225-1
	SULT1A1	NM_001394422.1		c.332T>G	p.Leu111Arg	missense	Exon 6 of 10	NP_001381351.1	P50225-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A1	ENST00000314752.12	TSL:1 MANE Select	c.332T>G	p.Leu111Arg	missense	Exon 4 of 8	ENSP00000321988.7	P50225-1
	SULT1A1	ENST00000569554.5	TSL:1	c.332T>G	p.Leu111Arg	missense	Exon 3 of 7	ENSP00000457912.1	P50225-1
	ENSG00000289755	ENST00000562058.5	TSL:1	n.1091T>G		non_coding_transcript_exon	Exon 6 of 10

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151756 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000242

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: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251270 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000589 AC: 86 AN: 1460474 Hom.: 3 Cov.: 30 AF XY: 0.0000537 AC XY: 39 AN XY: 726560

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.000179 AC: 8 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000639 AC: 71 AN: 1110806

Other (OTH) AF: 0.000116 AC: 7 AN: 60338

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151756 Hom.: 0 Cov.: 34 AF XY: 0.0000270 AC XY: 2 AN XY: 74098

African (AFR) AF: 0.0000242 AC: 1 AN: 41384

American (AMR) AF: 0.0000658 AC: 1 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67870

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.3
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.048	D
Polyphen		0.83	P
Vest4		0.63
MutPred		0.59		Gain of disorder (P = 0.0477)
MVP		0.40
MPC		0.063
ClinPred		0.80	D
GERP RS		2.2
Varity_R		0.69
gMVP		0.72
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs777884064; hg19: chr16-28619652;