chr2-108383419-G-T

Variant names:

• chr2-108383419-G-T
• rs775578071
• NM_006588.4:c.524G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006588.4(SULT1C4):​c.524G>T​(p.Cys175Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SULT1C4 NM_006588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2914697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1C4	NM_006588.4	c.524G>T	p.Cys175Phe	missense_variant	Exon 5 of 7	ENST00000272452.7	NP_006579.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1C4	ENST00000272452.7	c.524G>T	p.Cys175Phe	missense_variant	Exon 5 of 7	1	NM_006588.4	ENSP00000272452.2
SULT1C4	ENST00000409309.3	c.299G>T	p.Cys100Phe	missense_variant	Exon 3 of 5	1		ENSP00000387225.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251268 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135796

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461740 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.0
DANN	Benign	0.86
DEOGEN2	Benign	0.38	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.28	N;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.35
Sift	Benign	0.71	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.016	B;.
Vest4		0.44
MutPred		0.42		Gain of MoRF binding (P = 0.0713);.;
MVP		0.79
MPC		0.41
ClinPred		0.57	D
GERP RS		3.9
Varity_R		0.37
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs775578071; hg19: chr2-108999875;