Variant 6-75647788-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_015571.4(SENP6):c.537G>T(p.Arg179Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,612,190 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 65 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 66 hom. )

Consequence

SENP6
NM_015571.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.356

Variant links:

Genes affected

SENP6 (HGNC:20944): (SUMO specific peptidase 6) Ubiquitin-like molecules (UBLs), such as SUMO1 (UBL1; MIM 601912), are structurally related to ubiquitin (MIM 191339) and can be ligated to target proteins in a similar manner as ubiquitin. However, covalent attachment of UBLs does not result in degradation of the modified proteins. SUMO1 modification is implicated in the targeting of RANGAP1 (MIM 602362) to the nuclear pore complex, as well as in stabilization of I-kappa-B-alpha (NFKBIA; MIM 164008) from degradation by the 26S proteasome. Like ubiquitin, UBLs are synthesized as precursor proteins, with 1 or more amino acids following the C-terminal glycine-glycine residues of the mature UBL protein. Thus, the tail sequences of the UBL precursors need to be removed by UBL-specific proteases, such as SENP6, prior to their conjugation to target proteins (Kim et al., 2000 [PubMed 10799485]). SENPs also display isopeptidase activity for deconjugation of SUMO-conjugated substrates (Lima and Reverter, 2008 [PubMed 18799455]).[supplied by OMIM, Jun 2009]

SENP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 6-75647788-G-T is Benign according to our data. Variant chr6-75647788-G-T is described in ClinVar as [Benign]. Clinvar id is 768102.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.356 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SENP6	NM_015571.4 link	c.537G>T	p.Arg179Arg	synonymous_variant	7/24	ENST00000447266.7	NP_056386.2	Q9GZR1-1B3KMM0
SENP6	NM_001100409.3 link	c.516G>T	p.Arg172Arg	synonymous_variant	6/23		NP_001093879.1	Q9GZR1-2B3KMM0
SENP6	NM_001304792.2 link	c.516G>T	p.Arg172Arg	synonymous_variant	6/15		NP_001291721.1	Q9GZR1F8W6D9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SENP6	ENST00000447266.7 link	c.537G>T	p.Arg179Arg	synonymous_variant	7/24	1	NM_015571.4	ENSP00000402527.2		Q9GZR1-1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2388

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0553

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00397

AC:

989

AN:

249006

Hom.:

AF XY:

0.00263

AC XY:

355

AN XY:

135142

show subpopulations

Gnomad AFR exome

AF:

0.0582

Gnomad AMR exome

AF:

0.00192

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00162

AC:

2366

AN:

1459980

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

996

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.0575

Gnomad4 AMR exome

AF:

0.00247

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00415

GnomAD4 genome

AF:

0.0157

AC:

2395

AN:

152210

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1098

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0553

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00706

Hom.:

Bravo

AF:

0.0179

Asia WGS

AF:

0.00289

AC:

AN:

3476

EpiCase

AF:

0.000110

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.3

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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