NM_005500.3:c.257C>G

Variant names:

• chr19-47150248-C-G
• rs375709871
• NM_005500.3:c.257C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005500.3(SAE1):​c.257C>G​(p.Ser86Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. S86F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAE1 NM_005500.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.80
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAE1	NM_005500.3	MANE Select	c.257C>G	p.Ser86Cys	missense	Exon 3 of 9	NP_005491.1	Q9UBE0-1
	SAE1	NM_001145713.2		c.257C>G	p.Ser86Cys	missense	Exon 3 of 7	NP_001139185.1	Q9UBE0-3
	SAE1	NM_001145714.2		c.257C>G	p.Ser86Cys	missense	Exon 3 of 8	NP_001139186.1	Q9UBE0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAE1	ENST00000270225.12	TSL:1 MANE Select	c.257C>G	p.Ser86Cys	missense	Exon 3 of 9	ENSP00000270225.6	Q9UBE0-1
	SAE1	ENST00000906418.1		c.257C>G	p.Ser86Cys	missense	Exon 3 of 10	ENSP00000576477.1
	SAE1	ENST00000906417.1		c.257C>G	p.Ser86Cys	missense	Exon 3 of 10	ENSP00000576476.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.15
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.025	D
Polyphen		0.54	P
Vest4		0.40
MutPred		0.61		Loss of disorder (P = 0.0224)
MVP		0.25
MPC		0.31
ClinPred		0.85	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.79
gMVP		0.46
Mutation Taster		=40/60	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: rs375709871; hg19: chr19-47653505;