19-47122058-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000594144.5(SAE1):c.-173+8705T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 151,712 control chromosomes in the GnomAD database, including 48,084 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (48084 hom., cov: 29)
• Consequence: SAE1 ENST00000594144.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

Genes affected

SAE1 (HGNC:30660): (SUMO1 activating enzyme subunit 1) Posttranslational modification of proteins by the addition of the small protein SUMO (see SUMO1; MIM 601912), or sumoylation, regulates protein structure and intracellular localization. SAE1 and UBA2 (MIM 613295) form a heterodimer that functions as a SUMO-activating enzyme for the sumoylation of proteins (Okuma et al., 1999 [PubMed 9920803]).[supplied by OMIM, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAE1	ENST00000594144.5	c.-173+8705T>C		intron_variant		3
SAE1	ENST00000594526.5	c.-329-3038T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120524 AN: 151594 Hom.: 48030 Cov.: 29

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.780

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.795 AC: 120634 AN: 151712 Hom.: 48084 Cov.: 29 AF XY: 0.793 AC XY: 58773 AN XY: 74116

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.775

Alfa AF: 0.294 Hom.: 1441

Bravo AF: 0.804

Asia WGS AF: 0.679 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.43
Dann	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs309193; hg19: chr19-47625315;