rs71561434

Positions:

• chr6-75602002-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SENP6	NM_015571.4	c.-523C>T		5_prime_UTR_variant	1/24	ENST00000447266.7	NP_056386.2
SENP6	NM_001100409.3	c.-523C>T		5_prime_UTR_variant	1/23		NP_001093879.1
SENP6	NM_001304792.2	c.-523C>T		5_prime_UTR_variant	1/15		NP_001291721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SENP6	ENST00000447266	c.-523C>T		5_prime_UTR_variant	1/24	1	NM_015571.4	ENSP00000402527.2
SENP6	ENST00000370010	c.-523C>T		5_prime_UTR_variant	1/23	1		ENSP00000359027.2
SENP6	ENST00000327284	c.-523C>T		5_prime_UTR_variant	1/15	2		ENSP00000321820.8

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14508 AN: 151980 Hom.: 727 Cov.: 33

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.: 11 Cov.: 0 AF XY: 0.0968 AC XY: 110 AN XY: 1136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0833

Gnomad4 ASJ exome AF: 0.0357

Gnomad4 EAS exome AF: 0.0870

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0161

Gnomad4 NFE exome AF: 0.0930

Gnomad4 OTH exome AF: 0.0652

GnomAD4 genome AF: 0.0954 AC: 14516 AN: 152094 Hom.: 728 Cov.: 33 AF XY: 0.0958 AC XY: 7121 AN XY: 74342

Gnomad4 AFR AF: 0.0788

Gnomad4 AMR AF: 0.0894

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.0390

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0997

Alfa AF: 0.103 Hom.: 103

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	16
DANN	Benign	0.97
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

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

Other links and lift over

dbSNP: rs71561434; hg19: chr6-76311718;