rs2016874

Positions:

• chr21-44809258-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006936.3(SUMO3):​c.151-140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 780,170 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (38 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (14 hom.)
• Consequence: SUMO3 NM_006936.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

Genes affected

SUMO3 (HGNC:11124): (small ubiquitin like modifier 3) This gene encodes a member of the small ubiquitin-related modifier (SUMO) family of eukaryotic proteins. The encoded protein is covalently conjugated to other proteins via a post-translation modification known as sumoylation. Sumoylation may play a role in a wide variety of cellular processes, including nuclear transport, DNA replication and repair, mitosis, transcriptional regulation, and signal transduction. Alternatively spliced transcript variants encoding distinct proteins have been described. [provided by RefSeq, Feb 2014]

SUMO3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1910/152272) while in subpopulation AFR AF= 0.0432 (1796/41532). AF 95% confidence interval is 0.0416. There are 38 homozygotes in gnomad4. There are 895 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1910 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMO3	NM_006936.3	c.151-140T>C		intron_variant		ENST00000332859.11	NP_008867.2
SUMO3	NM_001286416.2	c.265-140T>C		intron_variant			NP_001273345.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMO3	ENST00000332859.11	c.151-140T>C		intron_variant		1	NM_006936.3	ENSP00000330343.7

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1906 AN: 152154 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00908

GnomAD4 exome AF: 0.00157 AC: 987 AN: 627898 Hom.: 14 AF XY: 0.00141 AC XY: 462 AN XY: 326568

Gnomad4 AFR exome AF: 0.0434

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000750

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000218

Gnomad4 OTH exome AF: 0.00307

GnomAD4 genome AF: 0.0125 AC: 1910 AN: 152272 Hom.: 38 Cov.: 33 AF XY: 0.0120 AC XY: 895 AN XY: 74462

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00978 Hom.: 0

Bravo AF: 0.0138

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.59

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: rs2016874; hg19: chr21-46229173;