rs375709871

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-47150248-C-G
• chr19-47150248-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAE1	NM_005500.3	c.257C>G	p.Ser86Cys	missense_variant	Exon 3 of 9	ENST00000270225.12	NP_005491.1
SAE1	NM_001145713.2	c.257C>G	p.Ser86Cys	missense_variant	Exon 3 of 7		NP_001139185.1
SAE1	NM_001145714.2	c.257C>G	p.Ser86Cys	missense_variant	Exon 3 of 8		NP_001139186.1
SAE1	NR_027280.2	n.437C>G		non_coding_transcript_exon_variant	Exon 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAE1	ENST00000270225.12	c.257C>G	p.Ser86Cys	missense_variant	Exon 3 of 9	1	NM_005500.3	ENSP00000270225.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.;.;.;T;T;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T;T;T;T;T;T;T;T
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	.;.;.;L;.;.;L;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.2	.;.;.;D;.;.;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0070	.;.;.;D;.;.;D;D
Sift4G	Uncertain	0.025	D;D;D;D;.;T;D;D
Polyphen		0.54	.;.;.;.;.;.;P;.
Vest4		0.40, 0.40, 0.41, 0.39
MutPred		0.61		.;.;.;Loss of disorder (P = 0.0224);.;Loss of disorder (P = 0.0224);Loss of disorder (P = 0.0224);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs375709871; hg19: chr19-47653505;