rs17414687

Variant names:

• chr6-75666836-G-A
• rs17414687
• NM_015571.4:c.1119G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-75666836-G-A
• chr6-75666836-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015571.4(SENP6):​c.1119G>A​(p.Ala373Ala) 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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SENP6	NM_015571.4	c.1119G>A	p.Ala373Ala	synonymous_variant	Exon 10 of 24	ENST00000447266.7	NP_056386.2
SENP6	NM_001100409.3	c.1098G>A	p.Ala366Ala	synonymous_variant	Exon 9 of 23		NP_001093879.1
SENP6	NM_001304792.2	c.1098G>A	p.Ala366Ala	synonymous_variant	Exon 9 of 15		NP_001291721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP6	ENST00000447266.7	c.1119G>A	p.Ala373Ala	synonymous_variant	Exon 10 of 24	1	NM_015571.4	ENSP00000402527.2

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

GnomAD2 exomes AF: 0.269 AC: 67049 AN: 249210 AF XY: 0.279

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 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

African (AFR) AF: 0.129 AC: 4330 AN: 33458

American (AMR) AF: 0.163 AC: 7283 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 7253 AN: 26116

East Asian (EAS) AF: 0.0342 AC: 1355 AN: 39666

South Asian (SAS) AF: 0.259 AC: 22337 AN: 86168

European-Finnish (FIN) AF: 0.281 AC: 14979 AN: 53376

Middle Eastern (MID) AF: 0.351 AC: 2023 AN: 5762

European-Non Finnish (NFE) AF: 0.370 AC: 410789 AN: 1110394

Other (OTH) AF: 0.306 AC: 18445 AN: 60322

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

African (AFR) AF: 0.133 AC: 5520 AN: 41512

American (AMR) AF: 0.222 AC: 3385 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3468

East Asian (EAS) AF: 0.0410 AC: 213 AN: 5190

South Asian (SAS) AF: 0.252 AC: 1214 AN: 4822

European-Finnish (FIN) AF: 0.285 AC: 3010 AN: 10568

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24868 AN: 67980

Other (OTH) AF: 0.262 AC: 552 AN: 2108

Alfa AF: 0.326 Hom.: 35962

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
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17414687; hg19: chr6-76376552; COSMIC: COSV108166882; COSMIC: COSV108166882;