19-47197285-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005500.3(SAE1):c.786T>C(p.Tyr262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,614,022 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0045 (52 hom.)
• Consequence: SAE1 NM_005500.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.38

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-47197285-T-C is Benign according to our data. Variant chr19-47197285-T-C is described in ClinVar as [Benign]. Clinvar id is 778848.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00285 (434/152276) while in subpopulation SAS AF= 0.0249 (120/4828). AF 95% confidence interval is 0.0212. There are 5 homozygotes in gnomad4. There are 237 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAE1	NM_005500.3	c.786T>C	p.Tyr262=	synonymous_variant	7/9	ENST00000270225.12
SAE1	NM_001145713.2	c.734-11874T>C		intron_variant
SAE1	NM_001145714.2	c.734-6386T>C		intron_variant
SAE1	NR_027280.2	n.966T>C		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAE1	ENST00000270225.12	c.786T>C	p.Tyr262=	synonymous_variant	7/9	1	NM_005500.3	P1

Frequencies

GnomAD3 genomes AF: 0.00285 AC: 433 AN: 152158 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00313

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00489 AC: 1230 AN: 251464 Hom.: 10 AF XY: 0.00606 AC XY: 824 AN XY: 135908

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00923

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0228

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00316

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00448 AC: 6548 AN: 1461746 Hom.: 52 Cov.: 32 AF XY: 0.00511 AC XY: 3713 AN XY: 727186

Gnomad4 AFR exome AF: 0.000687

Gnomad4 AMR exome AF: 0.000827

Gnomad4 ASJ exome AF: 0.00995

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0232

Gnomad4 FIN exome AF: 0.00103

Gnomad4 NFE exome AF: 0.00342

Gnomad4 OTH exome AF: 0.00447

GnomAD4 genome AF: 0.00285 AC: 434 AN: 152276 Hom.: 5 Cov.: 31 AF XY: 0.00318 AC XY: 237 AN XY: 74434

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.00313

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00360 Hom.: 1

Bravo AF: 0.00216

Asia WGS AF: 0.00982 AC: 35 AN: 3478

EpiCase AF: 0.00354

EpiControl AF: 0.00344

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.058
Dann	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs117605411; hg19: chr19-47700542; COSMIC: COSV54295482;