chr2-108378420-C-G

Position:

• chr2-108378420-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006588.4(SULT1C4):​c.83C>G​(p.Pro28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SULT1C4 NM_006588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16954404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT1C4	NM_006588.4	c.83C>G	p.Pro28Arg	missense_variant	1/7	ENST00000272452.7	NP_006579.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT1C4	ENST00000272452.7	c.83C>G	p.Pro28Arg	missense_variant	1/7	1	NM_006588.4	ENSP00000272452.2
SULT1C4	ENST00000409309.3	c.83C>G	p.Pro28Arg	missense_variant	1/5	1		ENSP00000387225.3
SULT1C4	ENST00000494122.1	n.510C>G		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.83C>G (p.P28R) alteration is located in exon 1 (coding exon 1) of the SULT1C4 gene. This alteration results from a C to G substitution at nucleotide position 83, causing the proline (P) at amino acid position 28 to be replaced by an arginine (R). 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	Pathogenic	0.64
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N;D
REVEL	Benign	0.090
Sift	Benign	0.32	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.99	D;.
Vest4		0.35
MutPred		0.47		Gain of MoRF binding (P = 0.0337);Gain of MoRF binding (P = 0.0337);
MVP		0.43
MPC		0.74
ClinPred		0.40	T
GERP RS		5.1
Varity_R		0.26
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-108994876;