rs145465524

Variant names:

• chr16-28592307-C-G
• rs145465524
• NM_001054.4:c.731G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-28592307-C-G
• chr16-28592307-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001054.4(SULT1A2):​c.731G>C​(p.Arg244Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000096 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R244H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: SULT1A2 NM_001054.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.47
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033283263).
• BP6: Variant 16-28592307-C-G is Benign according to our data. Variant chr16-28592307-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3323594.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A2	NM_001054.4	MANE Select	c.731G>C	p.Arg244Pro	missense	Exon 7 of 8	NP_001045.2	P50226
	SULT1A2	NM_001400258.1		c.731G>C	p.Arg244Pro	missense	Exon 8 of 9	NP_001387187.1	P50226
	SULT1A2	NM_001400259.1		c.731G>C	p.Arg244Pro	missense	Exon 8 of 9	NP_001387188.1	P50226

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A2	ENST00000335715.9	TSL:1 MANE Select	c.731G>C	p.Arg244Pro	missense	Exon 7 of 8	ENSP00000338742.4	P50226
	SULT1A2	ENST00000898358.1		c.881G>C	p.Arg294Pro	missense	Exon 6 of 7	ENSP00000568417.1
	SULT1A2	ENST00000898343.1		c.746G>C	p.Arg249Pro	missense	Exon 7 of 8	ENSP00000568402.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251168 AF XY: 0.0000663

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000958 AC: 140 AN: 1461664 Hom.: 0 Cov.: 79 AF XY: 0.000102 AC XY: 74 AN XY: 727146

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000108 AC: 120 AN: 1111838

Other (OTH) AF: 0.000132 AC: 8 AN: 60378

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74450

African (AFR) AF: 0.0000963 AC: 4 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10602

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68028

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

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.072
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.63
DANN	Benign	0.51
DEOGEN2	Benign	0.16	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.020	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-2.3	N
PhyloP100		3.5
PrimateAI	Benign	0.44	T
PROVEAN	Benign	6.5	N
REVEL	Benign	0.19
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.57		Loss of MoRF binding (P = 0.0223)
MVP		0.30
MPC		0.10
ClinPred		0.025	T
GERP RS		3.0
Varity_R		0.33
gMVP		0.58
Mutation Taster		=98/2	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: rs145465524; hg19: chr16-28603628;