16-28606814-C-G

Variant names:

• chr16-28606814-C-G
• rs777965756
• NM_001055.4:c.541G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001055.4(SULT1A1):​c.541G>C​(p.Glu181Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,460,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SULT1A1 NM_001055.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• Publications: 2 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27484876).

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.541G>C	p.Glu181Gln	missense	Exon 6 of 8	NP_001046.2
	SULT1A1	NM_001394421.1		c.541G>C	p.Glu181Gln	missense	Exon 9 of 11	NP_001381350.1	P50225-1
	SULT1A1	NM_001394422.1		c.541G>C	p.Glu181Gln	missense	Exon 8 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.541G>C	p.Glu181Gln	missense	Exon 6 of 8	ENSP00000321988.7	P50225-1
	SULT1A1	ENST00000569554.5	TSL:1	c.541G>C	p.Glu181Gln	missense	Exon 5 of 7	ENSP00000457912.1	P50225-1
	ENSG00000289755	ENST00000562058.5	TSL:1	n.1300G>C		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251232 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1460512 Hom.: 0 Cov.: 89 AF XY: 0.00000826 AC XY: 6 AN XY: 726590

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1110824

Other (OTH) AF: 0.0000497 AC: 3 AN: 60338

GnomAD4 genome Cov.: 36

Alfa AF: 0.000111 Hom.: 0

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.080
Sift	Benign	0.037	D
Sift4G	Benign	0.073	T
Polyphen		0.27	B
Vest4		0.50
MutPred		0.52		Gain of MoRF binding (P = 0.053)
MVP		0.44
MPC		0.033
ClinPred		0.42	T
GERP RS		1.4
Varity_R		0.53
gMVP		0.31
Mutation Taster		=80/20	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: rs777965756; hg19: chr16-28618135;