22-43833641-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014351.4(SULT4A1):c.602G>A(p.Arg201Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000333 in 1,593,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: SULT4A1 NM_014351.4 missense, splice_region
• Scores: Splicing: ADA: 0.8942
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.70

Genes affected

SULT4A1 (HGNC:14903): (sulfotransferase family 4A member 1) This gene encodes a member of the sulfotransferase family. The encoded protein is a brain-specific sulfotransferase believed to be involved in the metabolism of neurotransmitters. Polymorphisms in this gene may be associated with susceptibility to schizophrenia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16660193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT4A1	NM_014351.4	c.602G>A	p.Arg201Gln	missense_variant, splice_region_variant	5/7	ENST00000330884.9
SULT4A1	XM_047441321.1	c.602G>A	p.Arg201Gln	missense_variant, splice_region_variant	5/7
SULT4A1	XM_011530121.2	c.263G>A	p.Arg88Gln	missense_variant, splice_region_variant	2/4
SULT4A1	XM_047441322.1	c.263G>A	p.Arg88Gln	missense_variant, splice_region_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT4A1	ENST00000330884.9	c.602G>A	p.Arg201Gln	missense_variant, splice_region_variant	5/7	1	NM_014351.4	P1
SULT4A1	ENST00000422525.1	c.602G>A	p.Arg201Gln	missense_variant, splice_region_variant, NMD_transcript_variant	5/8	1
SULT4A1	ENST00000475131.1	n.141G>A		splice_region_variant, non_coding_transcript_exon_variant	2/3	4
SULT4A1	ENST00000432404.5	c.*243G>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	4/6	5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152200 Hom.: 0 Cov.: 33

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000499 AC: 11 AN: 220250 Hom.: 0 AF XY: 0.0000841 AC XY: 10 AN XY: 118840

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000600

Gnomad SAS exome AF: 0.000184

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000411

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000354 AC: 51 AN: 1441610 Hom.: 0 Cov.: 32 AF XY: 0.0000392 AC XY: 28 AN XY: 715092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000119

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.000144

Gnomad4 FIN exome AF: 0.0000197

Gnomad4 NFE exome AF: 0.0000263

Gnomad4 OTH exome AF: 0.0000502

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000302

ExAC AF: 0.0000661 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2022

The c.602G>A (p.R201Q) alteration is located in exon 5 (coding exon 5) of the SULT4A1 gene. This alteration results from a G to A substitution at nucleotide position 602, causing the arginine (R) at amino acid position 201 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.29
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.014
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.035	N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.23
Sift	Benign	0.22	T
Sift4G	Benign	0.12	T
Polyphen		0.0080	B
Vest4		0.37
MutPred		0.52		Loss of helix (P = 0.1299);
MVP		0.068
MPC		1.1
ClinPred		0.12	T
GERP RS		5.0
Varity_R		0.23
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.89
dbscSNV1_RF	Benign	0.64
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

Publications

LitVar

Other links and lift over

dbSNP: rs751151043; hg19: chr22-44229521;