2-108382415-C-A

Variant names:

• chr2-108382415-C-A
• rs1678430738
• NM_006588.4:c.326C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006588.4(SULT1C4):​c.326C>A​(p.Pro109Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SULT1C4 NM_006588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.35
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979

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.326C>A	p.Pro109Gln	missense	Exon 3 of 7	NP_006579.2
	SULT1C4	NM_001321770.2		c.295+528C>A		intron	N/A	NP_001308699.1	O75897-2
	SULT1C4	NR_135776.2		n.729+528C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1C4	ENST00000272452.7	TSL:1 MANE Select	c.326C>A	p.Pro109Gln	missense	Exon 3 of 7	ENSP00000272452.2	O75897-1
	SULT1C4	ENST00000409309.3	TSL:1	c.295+528C>A		intron	N/A	ENSP00000387225.3	O75897-2
	SULT1C4	ENST00000494122.1	TSL:1	n.1250C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Pathogenic	4.3	H
PhyloP100		6.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.90		Gain of solvent accessibility (P = 0.0374)
MVP		0.56
MPC		0.86
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.90
gMVP		0.77
Mutation Taster		=48/52	disease causing

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

Other links and lift over

dbSNP: rs1678430738; hg19: chr2-108998871;