rs759448103

Variant names:

• chr2-108378347-C-A
• rs759448103
• NM_006588.4:c.10C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-108378347-C-A
• chr2-108378347-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006588.4(SULT1C4):​c.10C>A​(p.His4Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. H4Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SULT1C4 NM_006588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 1 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_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033626705).

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.10C>A	p.His4Asn	missense	Exon 1 of 7	NP_006579.2
	SULT1C4	NM_001321770.2		c.10C>A	p.His4Asn	missense	Exon 1 of 5	NP_001308699.1	O75897-2
	SULT1C4	NR_135776.2		n.394C>A		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1C4	ENST00000272452.7	TSL:1 MANE Select	c.10C>A	p.His4Asn	missense	Exon 1 of 7	ENSP00000272452.2	O75897-1
	SULT1C4	ENST00000409309.3	TSL:1	c.10C>A	p.His4Asn	missense	Exon 1 of 5	ENSP00000387225.3	O75897-2
	SULT1C4	ENST00000494122.1	TSL:1	n.437C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461336 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726996

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111708

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.47
DANN	Benign	0.77
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.090
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.038
Sift	Benign	0.26	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.075
MutPred		0.18		Loss of disorder (P = 0.1285)
MVP		0.067
MPC		0.27
ClinPred		0.36	T
GERP RS		-0.83
PromoterAI		0.015	Neutral
Varity_R		0.068
gMVP		0.64
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs759448103; hg19: chr2-108994803;