NM_001055.4:c.493G>A

Variant names:

• chr16-28606957-C-T
• rs141878102
• NM_001055.4:c.493G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_001055.4(SULT1A1):​c.493G>A​(p.Gly165Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000299 in 1,612,482 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 36)
  • Exomes 𝑓: 0.00031 (16 hom.)
• Consequence: SULT1A1 NM_001055.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50
• 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: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802
• BS2: High Homozygotes in GnomAdExome4 at 16 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.493G>A	p.Gly165Arg	missense	Exon 5 of 8	NP_001046.2
	SULT1A1	NM_001394421.1		c.493G>A	p.Gly165Arg	missense	Exon 8 of 11	NP_001381350.1	P50225-1
	SULT1A1	NM_001394422.1		c.493G>A	p.Gly165Arg	missense	Exon 7 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.493G>A	p.Gly165Arg	missense	Exon 5 of 8	ENSP00000321988.7	P50225-1
	SULT1A1	ENST00000569554.5	TSL:1	c.493G>A	p.Gly165Arg	missense	Exon 4 of 7	ENSP00000457912.1	P50225-1
	ENSG00000289755	ENST00000562058.5	TSL:1	n.1252G>A		non_coding_transcript_exon	Exon 7 of 10

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 151886 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000119 AC: 30 AN: 251256 AF XY: 0.000125

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000312 AC: 456 AN: 1460478 Hom.: 16 Cov.: 53 AF XY: 0.000299 AC XY: 217 AN XY: 726568

African (AFR) AF: 0.000239 AC: 8 AN: 33466

American (AMR) AF: 0.0000224 AC: 1 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26114

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000361 AC: 401 AN: 1110792

Other (OTH) AF: 0.000679 AC: 41 AN: 60342

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152004 Hom.: 0 Cov.: 36 AF XY: 0.000148 AC XY: 11 AN XY: 74314

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000120 AC: 5 AN: 41530

American (AMR) AF: 0.0000656 AC: 1 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000280 AC: 19 AN: 67884

Other (OTH) AF: 0.00 AC: 0 AN: 2100

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000452683), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000102 Hom.: 0

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.0041	T
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	4.6	H
PhyloP100		5.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.91		Gain of MoRF binding (P = 0.0614)
MVP		0.77
MPC		0.070
ClinPred		1.0	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.94
gMVP		0.83
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs141878102; hg19: chr16-28618278; COSMIC: COSV59086815; COSMIC: COSV59086815;