NM_006588.4:c.419A>G

Variant names:

• chr2-108383118-A-G
• NM_006588.4:c.419A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006588.4(SULT1C4):​c.419A>G​(p.Lys140Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SULT1C4 NM_006588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006588.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1C4	NM_006588.4	MANE Select	c.419A>G	p.Lys140Arg	missense	Exon 4 of 7	NP_006579.2
	SULT1C4	NM_001321770.2		c.296-298A>G		intron	N/A	NP_001308699.1	O75897-2
	SULT1C4	NR_135776.2		n.730-298A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1C4	ENST00000272452.7	TSL:1 MANE Select	c.419A>G	p.Lys140Arg	missense	Exon 4 of 7	ENSP00000272452.2	O75897-1
	SULT1C4	ENST00000409309.3	TSL:1	c.296-298A>G		intron	N/A	ENSP00000387225.3	O75897-2
	SULT1C4	ENST00000957540.1		c.170-298A>G		intron	N/A	ENSP00000627599.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451970 Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1 AN XY: 720918

African (AFR) AF: 0.00 AC: 0 AN: 33162

American (AMR) AF: 0.0000230 AC: 1 AN: 43422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39462

South Asian (SAS) AF: 0.00 AC: 0 AN: 83114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107710

Other (OTH) AF: 0.00 AC: 0 AN: 60068

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.034	D
Polyphen		1.0	D
Vest4		0.44
MutPred		0.79		Loss of methylation at K140 (P = 0.0177)
MVP		0.90
MPC		0.81
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.84
gMVP		0.71
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr2-108999574;