21-44806982-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1557 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMO3	NM_006936.3	c.281C>T	p.Pro94Leu	missense_variant	Exon 4 of 4	ENST00000332859.11	NP_008867.2
SUMO3	NM_001286416.2	c.395C>T	p.Pro132Leu	missense_variant	Exon 4 of 4		NP_001273345.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMO3	ENST00000332859.11	c.281C>T	p.Pro94Leu	missense_variant	Exon 4 of 4	1	NM_006936.3	ENSP00000330343.7
SUMO3	ENST00000411651.6	c.395C>T	p.Pro132Leu	missense_variant	Exon 4 of 4	2		ENSP00000409666.2
SUMO3	ENST00000397898.7	c.331C>T	p.Arg111Trp	missense_variant	Exon 4 of 4	3		ENSP00000380995.3
SUMO3	ENST00000479153.1	n.371C>T		non_coding_transcript_exon_variant	Exon 4 of 4	2

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

GnomAD3 exomes AF: 0.00263 AC: 661 AN: 250960 Hom.: 9 AF XY: 0.00194 AC XY: 263 AN XY: 135708

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 SAS exome AF: 0.0000653

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

Gnomad4 AFR exome AF: 0.0393

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000200

Gnomad4 OTH exome AF: 0.00243

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

Gnomad4 AFR AF: 0.0353

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00193 Hom.: 4

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 02, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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;T
MetaRNN	Benign	0.0031	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.0070
Sift	Benign	0.15	T;D
Sift4G	Benign	0.25	T;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

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: rs112870818; hg19: chr21-46226897;