chr6-149400554-G-A

Position:

chr6-149400554-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001002255.2(SUMO4):c.163G>A(p.Val55Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,613,990 control chromosomes in the GnomAD database, including 216,559 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25727 hom., cov: 33)

Exomes 𝑓: 0.51 ( 190832 hom. )

Consequence

SUMO4
NM_001002255.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: 0.259

Variant links:

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]

SUMO4 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.982837E-7).

BP6

Variant 6-149400554-G-A is Benign according to our data. Variant chr6-149400554-G-A is described in ClinVar as [Benign]. Clinvar id is 2062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-149400554-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMO4	NM_001002255.2 linkuse as main transcript	c.163G>A	p.Val55Met	missense_variant	1/1	ENST00000326669.6	NP_001002255.1
TAB2	NM_001292034.3 linkuse as main transcript	c.1939+1370G>A		intron_variant		ENST00000637181.2	NP_001278963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMO4	ENST00000326669.6 linkuse as main transcript	c.163G>A	p.Val55Met	missense_variant	1/1		NM_001002255.2	ENSP00000318635	P1
TAB2	ENST00000637181.2 linkuse as main transcript	c.1939+1370G>A		intron_variant		1	NM_001292034.3	ENSP00000490618	P1	Q9NYJ8-1

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86908

AN:

152006

Hom.:

25691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.718

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.563

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.716

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.555

GnomAD3 exomes

AF:

0.554

AC:

139242

AN:

251486

Hom.:

39625

AF XY:

0.548

AC XY:

74482

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.725

Gnomad AMR exome

AF:

0.616

Gnomad ASJ exome

AF:

0.477

Gnomad EAS exome

AF:

0.719

Gnomad SAS exome

AF:

0.583

Gnomad FIN exome

AF:

0.531

Gnomad NFE exome

AF:

0.488

Gnomad OTH exome

AF:

0.532

GnomAD4 exome

AF:

0.507

AC:

741165

AN:

1461864

Hom.:

190832

Cov.:

AF XY:

0.508

AC XY:

369141

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.729

Gnomad4 AMR exome

AF:

0.614

Gnomad4 ASJ exome

AF:

0.474

Gnomad4 EAS exome

AF:

0.703

Gnomad4 SAS exome

AF:

0.577

Gnomad4 FIN exome

AF:

0.535

Gnomad4 NFE exome

AF:

0.482

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

AF:

0.572

AC:

87010

AN:

152126

Hom.:

25727

Cov.:

AF XY:

0.575

AC XY:

42742

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.718

Gnomad4 AMR

AF:

0.564

Gnomad4 ASJ

AF:

0.467

Gnomad4 EAS

AF:

0.715

Gnomad4 SAS

AF:

0.588

Gnomad4 FIN

AF:

0.536

Gnomad4 NFE

AF:

0.487

Gnomad4 OTH

AF:

0.560

Alfa

AF:

0.512

Hom.:

22532

Bravo

AF:

0.584

TwinsUK

AF:

0.496

AC:

1841

ALSPAC

AF:

0.483

AC:

1861

ESP6500AA

AF:

0.711

AC:

3134

ESP6500EA

AF:

0.485

AC:

4174

ExAC

AF:

0.555

AC:

67383

Asia WGS

AF:

0.717

AC:

2491

AN:

3478

EpiCase

AF:

0.482

EpiControl

AF:

0.485

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Type 1 diabetes mellitus 5

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 2005

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

This variant is associated with the following publications: (PMID: 25189908, 15247916, 21158221, 19915388, 20518843, 22884980, 19410319, 17130563) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.070

DANN

Benign

0.31

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.11

MetaRNN

Benign

0.0000010

MetaSVM

Benign

-0.97

MutationTaster

Benign

2.0e-7

P;P;P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

2.5

REVEL

Benign

0.079

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.036

MPC

0.057

ClinPred

0.0067

GERP RS

-0.47

gMVP

0.041

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over