2-108378352-C-G

Position:

• chr2-108378352-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006588.4(SULT1C4):​c.15C>G​(p.Asp5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,612,738 control chromosomes in the GnomAD database, including 75,108 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D5N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.39 (16119 hom., cov: 32)
  • Exomes 𝑓: 0.27 (58989 hom.)
• Consequence: SULT1C4 NM_006588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.924704E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT1C4	NM_006588.4	c.15C>G	p.Asp5Glu	missense_variant	1/7	ENST00000272452.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT1C4	ENST00000272452.7	c.15C>G	p.Asp5Glu	missense_variant	1/7	1	NM_006588.4	P1
SULT1C4	ENST00000409309.3	c.15C>G	p.Asp5Glu	missense_variant	1/5	1
SULT1C4	ENST00000494122.1	n.442C>G		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59613 AN: 151918 Hom.: 16061 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.348

GnomAD3 exomes AF: 0.283 AC: 71070 AN: 251050 Hom.: 13431 AF XY: 0.287 AC XY: 38877 AN XY: 135694

Gnomad AFR exome AF: 0.782

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.0712

Gnomad SAS exome AF: 0.415

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.266 AC: 387856 AN: 1460702 Hom.: 58989 Cov.: 33 AF XY: 0.269 AC XY: 195320 AN XY: 726716

Gnomad4 AFR exome AF: 0.794

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.393 AC: 59728 AN: 152036 Hom.: 16119 Cov.: 32 AF XY: 0.394 AC XY: 29323 AN XY: 74334

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.355

Alfa AF: 0.261 Hom.: 4709

Bravo AF: 0.393

TwinsUK AF: 0.250 AC: 926

ALSPAC AF: 0.237 AC: 912

ESP6500AA AF: 0.767 AC: 3378

ESP6500EA AF: 0.246 AC: 2118

ExAC AF: 0.298 AC: 36195

Asia WGS AF: 0.379 AC: 1319 AN: 3478

EpiCase AF: 0.242

EpiControl AF: 0.244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.26
DANN	Benign	0.60
DEOGEN2	Benign	0.0039	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.14	T;T
MetaRNN	Benign	9.9e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.71	N;N
REVEL	Benign	0.068
Sift	Benign	0.94	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.011
MutPred		0.062		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MPC		0.23
ClinPred		0.00089	T
GERP RS		-1.8
Varity_R		0.078
gMVP		0.65

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

Other links and lift over

dbSNP: rs1402467; hg19: chr2-108994808; COSMIC: COSV55597968;