21-44806982-G-T

Variant names:

• chr21-44806982-G-T
• rs112870818
• NM_006936.3:c.281C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006936.3(SUMO3):​c.281C>A​(p.Pro94Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. P94L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUMO3 NM_006936.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060616642).

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.281C>A	p.Pro94Gln	missense	Exon 4 of 4	NP_008867.2
	SUMO3	NM_001286416.2		c.395C>A	p.Pro132Gln	missense	Exon 4 of 4	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.281C>A	p.Pro94Gln	missense	Exon 4 of 4	ENSP00000330343.7	P55854-1
	SUMO3	ENST00000411651.6	TSL:2	c.395C>A	p.Pro132Gln	missense	Exon 4 of 4	ENSP00000409666.2	P55854-2
	SUMO3	ENST00000889599.1		c.323C>A	p.Pro108Gln	missense	Exon 4 of 4	ENSP00000559658.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.56
DANN	Benign	0.59
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.34
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.019
Sift	Benign	0.091	T
Sift4G	Benign	0.27	T
Polyphen		0.0080	B
Vest4		0.053
MutPred		0.11		Gain of solvent accessibility (P = 0.1505)
MVP		0.11
MPC		1.2
ClinPred		0.070	T
GERP RS		-2.4
Varity_R		0.074
gMVP		0.51
Mutation Taster		=97/3	polymorphism

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: rs112870818; hg19: chr21-46226897;