dbSNP rs646967: SENP6:c.52+8554C>T (chr6-75611130-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015571.4(SENP6):c.52+8554C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,958 control chromosomes in the GnomAD database, including 7,827 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 0.31 ( 7827 hom., cov: 32)

Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

SENP6
NM_015571.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.602

Publications

4 publications found

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:

ENSG00000293100 (HGNC:):

ENSG00000293100 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SENP6	NM_015571.4 link	c.52+8554C>T	intron_variant	Intron 1 of 23	ENST00000447266.7	NP_056386.2	Q9GZR1-1B3KMM0
LOC100421091		n.75611130C>T	intragenic_variant
SENP6	NM_001100409.3 link	c.52+8554C>T	intron_variant	Intron 1 of 22		NP_001093879.1	Q9GZR1-2B3KMM0
SENP6	NM_001304792.2 link	c.52+8554C>T	intron_variant	Intron 1 of 14		NP_001291721.1	Q9GZR1F8W6D9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP6	ENST00000447266.7 link	c.52+8554C>T		intron_variant	Intron 1 of 23	1	NM_015571.4	ENSP00000402527.2		Q9GZR1-1

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46783

AN:

151834

Hom.:

7826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.444

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.283

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.308

AC:

46806

AN:

151952

Hom.:

7827

Cov.:

AF XY:

0.312

AC XY:

23143

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.444

AC:

18394

AN:

41418

American (AMR)

AF:

0.236

AC:

3602

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

873

AN:

3470

East Asian (EAS)

AF:

0.275

AC:

1424

AN:

5180

South Asian (SAS)

AF:

0.393

AC:

1892

AN:

4814

European-Finnish (FIN)

AF:

0.307

AC:

3236

AN:

10538

Middle Eastern (MID)

AF:

0.277

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.242

AC:

16418

AN:

67932

Other (OTH)

AF:

0.279

AC:

590

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1594

3188

4783

6377

7971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.256

Hom.:

8827

Bravo

AF:

0.304

Asia WGS

AF:

0.306

AC:

1062

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.0

(source)

DANN

Benign

0.57

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over