Genetic Variant NM_006588.4:c.236G>A (chr2-108381828-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_006588.4(SULT1C4):c.236G>A(p.Arg79Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000848 in 1,497,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

SULT1C4
NM_006588.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

Variant links:

Genes affected

SULT1C4 (HGNC:11457): (sulfotransferase family 1C member 4) 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 a protein that belongs to the SULT1 subfamily, responsible for transferring a sulfo moiety from PAPS to phenol-containing compounds. [provided by RefSeq, Jul 2008]

SULT1C4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1C4	NM_006588.4 link	c.236G>A	p.Arg79Gln	missense_variant	Exon 2 of 7	ENST00000272452.7	NP_006579.2	O75897-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SULT1C4	ENST00000272452.7 link	c.236G>A	p.Arg79Gln	missense_variant	Exon 2 of 7	1	NM_006588.4	ENSP00000272452.2	O75897-1
SULT1C4	ENST00000409309.3 link	c.236G>A	p.Arg79Gln	missense_variant	Exon 2 of 5	1		ENSP00000387225.3	O75897-2
SULT1C4	ENST00000494122.1 link	n.663G>A		non_coding_transcript_exon_variant	Exon 2 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152070

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:

0.00142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000140

AC:

AN:

171840

Hom.:

AF XY:

0.000138

AC XY:

AN XY:

94232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000221

Gnomad FIN exome

AF:

0.000733

Gnomad NFE exome

AF:

0.0000586

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000788

AC:

106

AN:

1344934

Hom.:

Cov.:

AF XY:

0.0000694

AC XY:

AN XY:

663090

show subpopulations

Gnomad4 AFR exome

AF:

0.0000719

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000465

Gnomad4 EAS exome

AF:

0.0000288

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.000551

Gnomad4 NFE exome

AF:

0.0000595

Gnomad4 OTH exome

AF:

0.0000362

GnomAD4 genome

AF:

0.000138

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74400

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:

0.00142

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000300

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.236G>A (p.R79Q) alteration is located in exon 2 (coding exon 2) of the SULT1C4 gene. This alteration results from a G to A substitution at nucleotide position 236, causing the arginine (R) at amino acid position 79 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

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Uncertain

-0.046

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.40

Sift

Benign

0.052

T;T

Sift4G

Benign

0.073

T;T

Polyphen

1.0

D;.

Vest4

0.62

MVP

0.89

MPC

0.62

ClinPred

0.47

GERP RS

4.3

Varity_R

0.27

gMVP

0.55

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

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