16-28595639-T-A

Variant names:

• chr16-28595639-T-A
• rs4987024
• NM_001054.4:c.185A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001054.4(SULT1A2):​c.185A>T​(p.Tyr62Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,614,102 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0077 (6 hom., cov: 31)
  • Exomes 𝑓: 0.011 (59 hom.)
• Consequence: SULT1A2 NM_001054.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79
• Publications: 11 publications found

Genes affected

SULT1A2 (HGNC:11454): (sulfotransferase family 1A member 2) 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. Two alternatively spliced variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

ENSG00000288656 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005838901).
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001054.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A2	NM_001054.4	MANE Select	c.185A>T	p.Tyr62Phe	missense	Exon 3 of 8	NP_001045.2
	SULT1A2	NM_001400258.1		c.185A>T	p.Tyr62Phe	missense	Exon 4 of 9	NP_001387187.1
	SULT1A2	NM_001400259.1		c.185A>T	p.Tyr62Phe	missense	Exon 4 of 9	NP_001387188.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A2	ENST00000335715.9	TSL:1 MANE Select	c.185A>T	p.Tyr62Phe	missense	Exon 3 of 8	ENSP00000338742.4
	SULT1A2	ENST00000395630.5	TSL:5	c.185A>T	p.Tyr62Phe	missense	Exon 3 of 8	ENSP00000378992.1
	SULT1A2	ENST00000533150.5	TSL:2	c.185A>T	p.Tyr62Phe	missense	Exon 2 of 4	ENSP00000435271.1

Frequencies

GnomAD3 genomes AF: 0.00772 AC: 1174 AN: 152110 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00771

Gnomad SAS AF: 0.00830

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00961 AC: 2416 AN: 251448 AF XY: 0.00971

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00208

Gnomad EAS exome AF: 0.00614

Gnomad FIN exome AF: 0.0164

Gnomad NFE exome AF: 0.0128

Gnomad OTH exome AF: 0.00946

GnomAD4 exome AF: 0.0109 AC: 15996 AN: 1461874 Hom.: 59 Cov.: 32 AF XY: 0.0110 AC XY: 7983 AN XY: 727236

African (AFR) AF: 0.00188 AC: 63 AN: 33480

American (AMR) AF: 0.00228 AC: 102 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 54 AN: 26136

East Asian (EAS) AF: 0.00363 AC: 144 AN: 39700

South Asian (SAS) AF: 0.00852 AC: 735 AN: 86256

European-Finnish (FIN) AF: 0.0170 AC: 908 AN: 53420

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.0120 AC: 13372 AN: 1111994

Other (OTH) AF: 0.00982 AC: 593 AN: 60396

GnomAD4 genome AF: 0.00774 AC: 1178 AN: 152228 Hom.: 6 Cov.: 31 AF XY: 0.00750 AC XY: 558 AN XY: 74438

African (AFR) AF: 0.00173 AC: 72 AN: 41536

American (AMR) AF: 0.00314 AC: 48 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00772 AC: 40 AN: 5178

South Asian (SAS) AF: 0.00830 AC: 40 AN: 4818

European-Finnish (FIN) AF: 0.0160 AC: 170 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0115 AC: 781 AN: 68004

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00802 Hom.: 4

Bravo AF: 0.00647

TwinsUK AF: 0.00971 AC: 36

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.00802 AC: 69

ExAC AF: 0.0104 AC: 1268

Asia WGS AF: 0.0180 AC: 62 AN: 3478

EpiCase AF: 0.0101

EpiControl AF: 0.0108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.087
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.071
Sift	Uncertain	0.017	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.23
MPC		0.40
ClinPred		0.024	T
GERP RS		3.5
Varity_R		0.39
gMVP		0.48
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4987024; hg19: chr16-28606960; COSMIC: COSV57683351; COSMIC: COSV57683351;