NM_006936.3:c.281C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006936.3(SUMO3):​c.281C>T​(p.Pro94Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,614,052 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (21 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (21 hom.)
• Consequence: SUMO3 NM_006936.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.339
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031014085).
• BP6: Variant 21-44806982-G-A is Benign according to our data. Variant chr21-44806982-G-A is described in ClinVar as Benign. ClinVar VariationId is 789677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0102 (1557/152258) while in subpopulation AFR AF = 0.0353 (1468/41552). AF 95% confidence interval is 0.0338. There are 21 homozygotes in GnomAd4. There are 727 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1557 AD gene.

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>T	p.Pro94Leu	missense	Exon 4 of 4	NP_008867.2
	SUMO3	NM_001286416.2		c.395C>T	p.Pro132Leu	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>T	p.Pro94Leu	missense	Exon 4 of 4	ENSP00000330343.7	P55854-1
	SUMO3	ENST00000411651.6	TSL:2	c.395C>T	p.Pro132Leu	missense	Exon 4 of 4	ENSP00000409666.2	P55854-2
	SUMO3	ENST00000397898.7	TSL:3	c.331C>T	p.Arg111Trp	missense	Exon 4 of 4	ENSP00000380995.3	A8MUA9

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1554 AN: 152140 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00764

GnomAD2 exomes AF: 0.00263 AC: 661 AN: 250960 AF XY: 0.00194

Gnomad AFR exome AF: 0.0344

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000335

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00123 AC: 1801 AN: 1461794 Hom.: 21 Cov.: 31 AF XY: 0.00113 AC XY: 820 AN XY: 727186

African (AFR) AF: 0.0393 AC: 1314 AN: 33472

American (AMR) AF: 0.00208 AC: 93 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.000200 AC: 222 AN: 1112000

Other (OTH) AF: 0.00243 AC: 147 AN: 60392

GnomAD4 genome AF: 0.0102 AC: 1557 AN: 152258 Hom.: 21 Cov.: 32 AF XY: 0.00977 AC XY: 727 AN XY: 74446

African (AFR) AF: 0.0353 AC: 1468 AN: 41552

American (AMR) AF: 0.00301 AC: 46 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68020

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00392 Hom.: 12

Bravo AF: 0.0115

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0322 AC: 142

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00331 AC: 402

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.1
DANN	Benign	0.60
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.34
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.0070
Sift	Benign	0.15	T
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.048
MVP		0.31
MPC		1.3
ClinPred		0.00033	T
GERP RS		-2.4
Varity_R		0.069
gMVP		0.53
Mutation Taster		=98/2	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;