21-44809478-C-T

Variant names:

• chr21-44809478-C-T
• rs2017089
• NM_006936.3:c.151-360G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006936.3(SUMO3):​c.151-360G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,184 control chromosomes in the GnomAD database, including 1,120 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 0.10 (1120 hom., cov: 32)
• Consequence: SUMO3 NM_006936.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006936.3. 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
	SUMO3	NM_006936.3	MANE Select	c.151-360G>A		intron	N/A	NP_008867.2
	SUMO3	NM_001286416.2		c.265-360G>A		intron	N/A	NP_001273345.1	P55854-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMO3	ENST00000332859.11	TSL:1 MANE Select	c.151-360G>A		intron	N/A	ENSP00000330343.7	P55854-1
	SUMO3	ENST00000397893.3	TSL:2	c.151-360G>A		intron	N/A	ENSP00000380990.3	A8MU27
	SUMO3	ENST00000411651.6	TSL:2	c.265-360G>A		intron	N/A	ENSP00000409666.2	P55854-2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15780 AN: 152066 Hom.: 1117 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15793 AN: 152184 Hom.: 1120 Cov.: 32 AF XY: 0.0992 AC XY: 7385 AN XY: 74444

African (AFR) AF: 0.0329 AC: 1365 AN: 41518

American (AMR) AF: 0.114 AC: 1746 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3466

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0794 AC: 383 AN: 4824

European-Finnish (FIN) AF: 0.0774 AC: 821 AN: 10604

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10498 AN: 67988

Other (OTH) AF: 0.142 AC: 299 AN: 2110

Alfa AF: 0.140 Hom.: 790

Bravo AF: 0.103

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.1
DANN	Benign	0.70
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs2017089; hg19: chr21-46229393;