chr21-44807021-T-C

Position:

• chr21-44807021-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006936.3(SUMO3):​c.242A>G​(p.Asp81Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUMO3 NM_006936.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.23

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMO3	NM_006936.3	c.242A>G	p.Asp81Gly	missense_variant	4/4	ENST00000332859.11	NP_008867.2
SUMO3	NM_001286416.2	c.356A>G	p.Asp119Gly	missense_variant	4/4		NP_001273345.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMO3	ENST00000332859.11	c.242A>G	p.Asp81Gly	missense_variant	4/4	1	NM_006936.3	ENSP00000330343.7
SUMO3	ENST00000411651.6	c.356A>G	p.Asp119Gly	missense_variant	4/4	2		ENSP00000409666.2
SUMO3	ENST00000397898.7	c.292A>G	p.Thr98Ala	missense_variant	4/4	3		ENSP00000380995.3
SUMO3	ENST00000479153.1	n.332A>G		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2024

The c.242A>G (p.D81G) alteration is located in exon 4 (coding exon 4) of the SUMO3 gene. This alteration results from a A to G substitution at nucleotide position 242, causing the aspartic acid (D) at amino acid position 81 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.85	P;.
Vest4		0.91
MutPred		0.76		Loss of stability (P = 0.0199);.;
MVP		0.81
MPC		2.3
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.93
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-46226936;