6-149400829-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMO4	NM_001002255.2	c.*150T>C		3_prime_UTR_variant	Exon 1 of 1	ENST00000326669.6	NP_001002255.1
TAB2	NM_001292034.3	c.1939+1645T>C		intron_variant	Intron 6 of 6	ENST00000637181.2	NP_001278963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMO4	ENST00000326669.6	c.*150T>C		3_prime_UTR_variant	Exon 1 of 1	6	NM_001002255.2	ENSP00000318635.4
TAB2	ENST00000637181.2	c.1939+1645T>C		intron_variant	Intron 6 of 6	1	NM_001292034.3	ENSP00000490618.1

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

Gnomad4 AFR exome AF: 0.905

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.699

Gnomad4 SAS exome AF: 0.577

Gnomad4 FIN exome AF: 0.537

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.540

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

Gnomad4 AFR AF: 0.901

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.602

Alfa AF: 0.555 Hom.: 11630

Bravo AF: 0.645

Asia WGS AF: 0.725 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.4
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs237024; hg19: chr6-149721965;