NM_005500.3:c.251C>G

Variant names:

• chr19-47150242-C-G
• rs757486381
• NM_005500.3:c.251C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005500.3(SAE1):​c.251C>G​(p.Thr84Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. T84N) 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: 0.509
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10231772).

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.251C>G	p.Thr84Ser	missense	Exon 3 of 9	NP_005491.1	Q9UBE0-1
	SAE1	NM_001145713.2		c.251C>G	p.Thr84Ser	missense	Exon 3 of 7	NP_001139185.1	Q9UBE0-3
	SAE1	NM_001145714.2		c.251C>G	p.Thr84Ser	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.251C>G	p.Thr84Ser	missense	Exon 3 of 9	ENSP00000270225.6	Q9UBE0-1
	SAE1	ENST00000906418.1		c.251C>G	p.Thr84Ser	missense	Exon 3 of 10	ENSP00000576477.1
	SAE1	ENST00000906417.1		c.251C>G	p.Thr84Ser	missense	Exon 3 of 10	ENSP00000576476.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.46	N
PhyloP100		0.51
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.073
Sift	Benign	0.18	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.38		Gain of disorder (P = 0.041)
MVP		0.36
MPC		0.17
ClinPred		0.35	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.17
Mutation Taster		=296/4	polymorphism

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: rs757486381; hg19: chr19-47653499;