NM_005420.3:c.407T>G

Variant names:

• chr4-69849526-A-C
• rs75140571
• NM_005420.3:c.407T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP3 BP4_Moderate

The NM_005420.3(SULT1E1):​c.407T>G​(p.Val136Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. V136I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SULT1E1 NM_005420.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78
• Publications: 1 publications found

Genes affected

SULT1E1 (HGNC:11377): (sulfotransferase family 1E member 1) 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 transfers a sulfo moiety to and from estrone, which may control levels of estrogen receptors. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Eigen, MutationAssessor, PROVEAN, REVEL, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster, PrimateAI was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.16618964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005420.3. 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
	SULT1E1	NM_005420.3	MANE Select	c.407T>G	p.Val136Gly	missense	Exon 5 of 8	NP_005411.1	Q53X91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1E1	ENST00000226444.4	TSL:1 MANE Select	c.407T>G	p.Val136Gly	missense	Exon 5 of 8	ENSP00000226444.3	P49888
	SULT1E1	ENST00000504002.1	TSL:1	n.513T>G		non_coding_transcript_exon	Exon 5 of 5
	SULT1E1	ENST00000904222.1		c.455T>G	p.Val152Gly	missense	Exon 6 of 9	ENSP00000574281.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000426 AC: 106 AN: 249018 AF XY: 0.000230

Gnomad AFR exome AF: 0.00203

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.000273

Gnomad FIN exome AF: 0.000279

Gnomad NFE exome AF: 0.000470

Gnomad OTH exome AF: 0.000992

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000891 AC: 13 AN: 1458806 Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7 AN XY: 725770

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33342

American (AMR) AF: 0.00 AC: 0 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 86052

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110072

Other (OTH) AF: 0.00 AC: 0 AN: 60232

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00204 AC: 248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.95	D
Eigen	Pathogenic	0.80
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.17	T
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Pathogenic	4.4	H
PhyloP100		5.8
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Pathogenic	0.88
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.013	D
Polyphen		0.97	D
Vest4		0.54
MVP		0.93
MPC		0.63
ClinPred		0.15	T
GERP RS		3.8
Varity_R		0.93
gMVP		0.85
Mutation Taster		=17/83	disease causing

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: rs75140571; hg19: chr4-70715244;