19-47158236-G-A

Variant names:

• chr19-47158236-G-A
• rs307896
• NM_005500.3:c.627+3023G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005500.3(SAE1):​c.627+3023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,034 control chromosomes in the GnomAD database, including 3,652 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 0.19 (3652 hom., cov: 32)
• Consequence: SAE1 NM_005500.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 34 publications found

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]

LOC124904730 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005500.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAE1	NM_005500.3	MANE Select	c.627+3023G>A		intron	N/A	NP_005491.1
	SAE1	NM_001145713.2		c.627+3023G>A		intron	N/A	NP_001139185.1
	SAE1	NM_001145714.2		c.627+3023G>A		intron	N/A	NP_001139186.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAE1	ENST00000270225.12	TSL:1 MANE Select	c.627+3023G>A		intron	N/A	ENSP00000270225.6
	SAE1	ENST00000413379.7	TSL:2	c.627+3023G>A		intron	N/A	ENSP00000416557.2
	SAE1	ENST00000392776.3	TSL:3	c.627+3023G>A		intron	N/A	ENSP00000440818.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28992 AN: 151916 Hom.: 3653 Cov.: 32

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.191 AC: 28982 AN: 152034 Hom.: 3652 Cov.: 32 AF XY: 0.185 AC XY: 13730 AN XY: 74272

African (AFR) AF: 0.0511 AC: 2121 AN: 41498

American (AMR) AF: 0.169 AC: 2577 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3462

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.0779 AC: 376 AN: 4826

European-Finnish (FIN) AF: 0.256 AC: 2700 AN: 10528

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19662 AN: 67970

Other (OTH) AF: 0.204 AC: 430 AN: 2110

Alfa AF: 0.252 Hom.: 16116

Bravo AF: 0.180

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.5
DANN	Benign	0.67
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs307896; hg19: chr19-47661493;