Genetic Variant NM_014351.4:c.602G>A (chr22-43833641-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Variant links:

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]

SULT4A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SULT4A1	NM_014351.4 link	c.602G>A	p.Arg201Gln	missense_variant, splice_region_variant	Exon 5 of 7	ENST00000330884.9	NP_055166.1	Q9BR01-1
SULT4A1	XM_047441321.1 link	c.602G>A	p.Arg201Gln	missense_variant, splice_region_variant	Exon 5 of 7		XP_047297277.1
SULT4A1	XM_011530121.2 link	c.263G>A	p.Arg88Gln	missense_variant, splice_region_variant	Exon 2 of 4		XP_011528423.1	B7Z2E1
SULT4A1	XM_047441322.1 link	c.263G>A	p.Arg88Gln	missense_variant, splice_region_variant	Exon 2 of 4		XP_047297278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT4A1	ENST00000330884.9 link	c.602G>A	p.Arg201Gln	missense_variant, splice_region_variant	Exon 5 of 7	1	NM_014351.4	ENSP00000332565.4		Q9BR01-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

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:

AN:

220250

Hom.:

AF XY:

0.0000841

AC XY:

AN XY:

118840

show subpopulations

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:

AN:

1441610

Hom.:

Cov.:

AF XY:

0.0000392

AC XY:

AN XY:

715092

show subpopulations

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:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

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:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

-0.014

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.068

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.035

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.37

REVEL

Benign

0.23

Sift

Benign

0.22

Sift4G

Benign

0.12

Polyphen

0.0080

Vest4

0.37

MutPred

0.52

Loss of helix (P = 0.1299);

MVP

0.068

MPC

1.1

ClinPred

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over