rs199882807

Variant names:

• chr2-108381828-G-A
• rs199882807
• NM_006588.4:c.236G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006588.4(SULT1C4):​c.236G>A​(p.Arg79Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000848 in 1,497,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: SULT1C4 NM_006588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16
• Publications: 5 publications found

Genes affected

SULT1C4 (HGNC:11457): (sulfotransferase family 1C member 4) 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 a protein that belongs to the SULT1 subfamily, responsible for transferring a sulfo moiety from PAPS to phenol-containing compounds. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006588.4. 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
	SULT1C4	NM_006588.4	MANE Select	c.236G>A	p.Arg79Gln	missense	Exon 2 of 7	NP_006579.2
	SULT1C4	NM_001321770.2		c.236G>A	p.Arg79Gln	missense	Exon 2 of 5	NP_001308699.1	O75897-2
	SULT1C4	NR_135776.2		n.670G>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1C4	ENST00000272452.7	TSL:1 MANE Select	c.236G>A	p.Arg79Gln	missense	Exon 2 of 7	ENSP00000272452.2	O75897-1
	SULT1C4	ENST00000409309.3	TSL:1	c.236G>A	p.Arg79Gln	missense	Exon 2 of 5	ENSP00000387225.3	O75897-2
	SULT1C4	ENST00000494122.1	TSL:1	n.663G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152070 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000140 AC: 24 AN: 171840 AF XY: 0.000138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000169

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000733

Gnomad NFE exome AF: 0.0000586

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000788 AC: 106 AN: 1344934 Hom.: 0 Cov.: 30 AF XY: 0.0000694 AC XY: 46 AN XY: 663090

African (AFR) AF: 0.0000719 AC: 2 AN: 27812

American (AMR) AF: 0.00 AC: 0 AN: 25158

Ashkenazi Jewish (ASJ) AF: 0.0000465 AC: 1 AN: 21522

East Asian (EAS) AF: 0.0000288 AC: 1 AN: 34776

South Asian (SAS) AF: 0.000139 AC: 9 AN: 64772

European-Finnish (FIN) AF: 0.000551 AC: 28 AN: 50832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5332

European-Non Finnish (NFE) AF: 0.0000595 AC: 63 AN: 1059412

Other (OTH) AF: 0.0000362 AC: 2 AN: 55318

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74400

African (AFR) AF: 0.00 AC: 0 AN: 41524

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00142 AC: 15 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000300 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	20
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	-0.046	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.2
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.40
Sift	Benign	0.052	T
Sift4G	Benign	0.073	T
Polyphen		1.0	D
Vest4		0.62
MVP		0.89
MPC		0.62
ClinPred		0.47	T
GERP RS		4.3
Varity_R		0.27
gMVP		0.55
Mutation Taster		=77/23	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: rs199882807; hg19: chr2-108998284; COSMIC: COSV55597462;