chr19-47150242-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005500.3(SAE1):​c.251C>A​(p.Thr84Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,552 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (1 hom.)
• Consequence: SAE1 NM_005500.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07495168).

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>A	p.Thr84Asn	missense	Exon 3 of 9	NP_005491.1	Q9UBE0-1
	SAE1	NM_001145713.2		c.251C>A	p.Thr84Asn	missense	Exon 3 of 7	NP_001139185.1	Q9UBE0-3
	SAE1	NM_001145714.2		c.251C>A	p.Thr84Asn	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>A	p.Thr84Asn	missense	Exon 3 of 9	ENSP00000270225.6	Q9UBE0-1
	SAE1	ENST00000600753.1	TSL:4	c.-62C>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000469978.1	M0QYP2
	SAE1	ENST00000906418.1		c.251C>A	p.Thr84Asn	missense	Exon 3 of 10	ENSP00000576477.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000559 AC: 14 AN: 250574 AF XY: 0.0000664

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000408

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460416 Hom.: 1 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 726534

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.000360 AC: 16 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5394

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111576

Other (OTH) AF: 0.00 AC: 0 AN: 60302

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.000197 AC: 3 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000868 Hom.: 1

Bravo AF: 0.0000264

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.79	N
PhyloP100		0.51
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.043
Sift	Benign	0.14	T
Sift4G	Benign	0.32	T
Polyphen		0.0020	B
Vest4		0.39
MutPred		0.37		Loss of MoRF binding (P = 0.1341)
MVP		0.40
MPC		0.28
ClinPred		0.088	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.43
gMVP		0.30
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;