6-149400829-T-C

Variant names:

• chr6-149400829-T-C
• rs237024
• NM_001002255.2:c.*150T>C

Variant summary

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

The NM_001002255.2(SUMO4):​c.*150T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 865,862 control chromosomes in the GnomAD database, including 130,037 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 0.63 (32320 hom., cov: 33)
  • Exomes 𝑓: 0.52 (97717 hom.)
• Consequence: SUMO4 NM_001002255.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 20 publications found

Genes affected

SUMO4 (HGNC:21181): (small ubiquitin like modifier 4) This gene is a member of the SUMO gene family. This family of genes encode small ubiquitin-related modifiers that are attached to proteins and control the target proteins' subcellular localization, stability, or activity. The protein described in this record is located in the cytoplasm and specifically modifies IKBA, leading to negative regulation of NF-kappa-B-dependent transcription of the IL12B gene. A specific polymorphism in this SUMO gene, which leads to the M55V substitution, has been associated with type I diabetes. The RefSeq contains this polymorphism. [provided by RefSeq, Jul 2008]

TAB2 (HGNC:17075): (TGF-beta activated kinase 1 (MAP3K7) binding protein 2) The protein encoded by this gene is an activator of MAP3K7/TAK1, which is required for for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK. This protein forms a kinase complex with TRAF6, MAP3K7 and TAB1, and it thus serves as an adaptor that links MAP3K7 and TRAF6. This protein, along with TAB1 and MAP3K7, also participates in the signal transduction induced by TNFSF11/RANKl through the activation of the receptor activator of NF-kappaB (TNFRSF11A/RANK), which may regulate the development and function of osteoclasts. Studies of the related mouse protein indicate that it functions to protect against liver damage caused by chemical stressors. Mutations in this gene cause congenital heart defects, multiple types, 2 (CHTD2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

TAB2 Gene-Disease associations (from GenCC):

• chromosome 6q24-q25 deletion syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• congenital heart defects, multiple types, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• polyvalvular heart disease syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002255.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMO4	NM_001002255.2	MANE Select	c.*150T>C		3_prime_UTR	Exon 1 of 1	NP_001002255.1
	TAB2	NM_001292034.3	MANE Select	c.1939+1645T>C		intron	N/A	NP_001278963.1
	TAB2	NM_001369506.1		c.1939+1645T>C		intron	N/A	NP_001356435.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMO4	ENST00000326669.6	TSL:6 MANE Select	c.*150T>C		3_prime_UTR	Exon 1 of 1	ENSP00000318635.4
	TAB2	ENST00000637181.2	TSL:1 MANE Select	c.1939+1645T>C		intron	N/A	ENSP00000490618.1
	TAB2	ENST00000470466.5	TSL:1	n.*538+1645T>C		intron	N/A	ENSP00000432709.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95148 AN: 152038 Hom.: 32261 Cov.: 33

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.516 AC: 368179 AN: 713706 Hom.: 97717 Cov.: 9 AF XY: 0.517 AC XY: 188612 AN XY: 365038

African (AFR) AF: 0.905 AC: 15288 AN: 16902

American (AMR) AF: 0.599 AC: 11519 AN: 19236

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 7410 AN: 15364

East Asian (EAS) AF: 0.699 AC: 23004 AN: 32890

South Asian (SAS) AF: 0.577 AC: 28727 AN: 49758

European-Finnish (FIN) AF: 0.537 AC: 24464 AN: 45570

Middle Eastern (MID) AF: 0.470 AC: 1184 AN: 2518

European-Non Finnish (NFE) AF: 0.479 AC: 237970 AN: 497010

Other (OTH) AF: 0.540 AC: 18613 AN: 34458

GnomAD4 genome AF: 0.626 AC: 95272 AN: 152156 Hom.: 32320 Cov.: 33 AF XY: 0.627 AC XY: 46666 AN XY: 74382

African (AFR) AF: 0.901 AC: 37426 AN: 41544

American (AMR) AF: 0.586 AC: 8958 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3472

East Asian (EAS) AF: 0.716 AC: 3703 AN: 5174

South Asian (SAS) AF: 0.588 AC: 2839 AN: 4828

European-Finnish (FIN) AF: 0.535 AC: 5650 AN: 10566

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33278 AN: 67966

Other (OTH) AF: 0.602 AC: 1271 AN: 2112

Alfa AF: 0.561 Hom.: 13883

Bravo AF: 0.645

Asia WGS AF: 0.725 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.4
DANN	Benign	0.73
PhyloP100		-0.013
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs237024; hg19: chr6-149721965;