19-47122058-T-C

Variant names:

• chr19-47122058-T-C
• rs309193
• ENST00000594144.5:c.-173+8705T>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAE1	ENST00000594144.5	c.-173+8705T>C		intron_variant	Intron 1 of 6	3		ENSP00000471010.1
SAE1	ENST00000594526.5	c.-329-3038T>C		intron_variant	Intron 1 of 4	3		ENSP00000472389.1

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;