16-28608517-C-G

Variant names:

• chr16-28608517-C-G
• rs375616347
• NM_001055.4:c.235G>C

Variant summary

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

The NM_001055.4(SULT1A1):​c.235G>C​(p.Val79Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,460,526 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: SULT1A1 NM_001055.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

Genes affected

SULT1A1 (HGNC:11453): (sulfotransferase family 1A 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 one of two phenol sulfotransferases with thermostable enzyme activity. Multiple alternatively spliced variants that encode two isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ENSG00000289755 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1A1	NM_001055.4	c.235G>C	p.Val79Leu	missense_variant	Exon 3 of 8	ENST00000314752.12	NP_001046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1A1	ENST00000314752.12	c.235G>C	p.Val79Leu	missense_variant	Exon 3 of 8	1	NM_001055.4	ENSP00000321988.7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251230 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135792

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000452 AC: 66 AN: 1460526 Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30 AN XY: 726594

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000585

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000165 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;T;T;T;.
Eigen	Benign	-0.027
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.84	.;T;.;.;D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.7	M;M;M;M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Pathogenic	0.67
Sift	Benign	0.12	T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;.
Polyphen		0.92	P;P;P;P;.
Vest4		0.47
MutPred		0.67		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.87
MPC		0.040
ClinPred		0.61	D
GERP RS		1.4
Varity_R		0.68
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs375616347; hg19: chr16-28619838;