Genetic Variant NM_015571.4:c.-523C>T (chr6-75602002-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.-523C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 153,900 control chromosomes in the GnomAD database, including 739 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 0.095 ( 728 hom., cov: 33)

Exomes 𝑓: 0.087 ( 11 hom. )

Consequence

SENP6
NM_015571.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.804

Publications

7 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:

ENSG00000297132 (HGNC:):

ENSG00000297132 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=-0.48).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SENP6	NM_015571.4 link	c.-523C>T	5_prime_UTR_variant	Exon 1 of 24	ENST00000447266.7	NP_056386.2	Q9GZR1-1B3KMM0
SENP6	NM_001100409.3 link	c.-523C>T	5_prime_UTR_variant	Exon 1 of 23		NP_001093879.1	Q9GZR1-2B3KMM0
SENP6	NM_001304792.2 link	c.-523C>T	5_prime_UTR_variant	Exon 1 of 15		NP_001291721.1	Q9GZR1F8W6D9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP6	ENST00000447266.7 link	c.-523C>T		5_prime_UTR_variant	Exon 1 of 24	1	NM_015571.4	ENSP00000402527.2		Q9GZR1-1

Frequencies

GnomAD3 genomes

AF:

0.0955

AC:

14508

AN:

151980

Hom.:

727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0787

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.0895

Gnomad ASJ

AF:

0.0939

Gnomad EAS

AF:

0.0387

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.102

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.0875

AC:

158

AN:

1806

Hom.:

Cov.:

AF XY:

0.0968

AC XY:

110

AN XY:

1136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0833

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0357

AC:

AN:

East Asian (EAS)

AF:

0.0870

AC:

AN:

South Asian (SAS)

AF:

0.104

AC:

AN:

212

European-Finnish (FIN)

AF:

0.0161

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0930

AC:

122

AN:

1312

Other (OTH)

AF:

0.0652

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0954

AC:

14516

AN:

152094

Hom.:

728

Cov.:

AF XY:

0.0958

AC XY:

7121

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0788

AC:

3272

AN:

41532

American (AMR)

AF:

0.0894

AC:

1368

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0939

AC:

326

AN:

3470

East Asian (EAS)

AF:

0.0390

AC:

201

AN:

5156

South Asian (SAS)

AF:

0.102

AC:

494

AN:

4822

European-Finnish (FIN)

AF:

0.127

AC:

1344

AN:

10554

Middle Eastern (MID)

AF:

0.0959

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.106

AC:

7183

AN:

67944

Other (OTH)

AF:

0.0997

AC:

211

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

668

1337

2005

2674

3342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.103

Hom.:

106

Bravo

AF:

0.0891

Asia WGS

AF:

0.0700

AC:

243

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.80

PromoterAI

-0.017

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over