rs17414687

chr6-75666836-G-Achr6-75666836-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015571.4(SENP6):c.1119G>A(p.Ala373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,612,104 control chromosomes in the GnomAD database, including 93,170 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 0.26 (6241 hom., cov: 32)
  • Exomes 𝑓: 0.33 (86929 hom.)
• Consequence: SENP6 NM_015571.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.472 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SENP6	NM_015571.4	c.1119G>A	p.Ala373=	synonymous_variant	10/24	ENST00000447266.7
SENP6	NM_001100409.3	c.1098G>A	p.Ala366=	synonymous_variant	9/23
SENP6	NM_001304792.2	c.1098G>A	p.Ala366=	synonymous_variant	9/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SENP6	ENST00000447266.7	c.1119G>A	p.Ala373=	synonymous_variant	10/24	1	NM_015571.4	P2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40152 AN: 152010 Hom.: 6243 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.265

GnomAD3 exomes AF: 0.269 AC: 67049 AN: 249210 Hom.: 10651 AF XY: 0.279 AC XY: 37718 AN XY: 135198

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.0374

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.277

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.335 AC: 488794 AN: 1459976 Hom.: 86929 Cov.: 33 AF XY: 0.334 AC XY: 242414 AN XY: 726426

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.0342

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.264 AC: 40143 AN: 152128 Hom.: 6241 Cov.: 32 AF XY: 0.258 AC XY: 19155 AN XY: 74378

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.0410

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.262

Alfa AF: 0.331 Hom.: 17222

Bravo AF: 0.251

Asia WGS AF: 0.146 AC: 513 AN: 3478

EpiCase AF: 0.358

EpiControl AF: 0.361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.1
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17414687; hg19: chr6-76376552;