rs646967

Variant names:

• chr6-75611130-C-T
• rs646967
• NM_015571.4:c.52+8554C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 4 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]

ENSG00000293100 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015571.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENP6	NM_015571.4	MANE Select	c.52+8554C>T		intron	N/A	NP_056386.2	Q9GZR1-1
	SENP6	NM_001100409.3		c.52+8554C>T		intron	N/A	NP_001093879.1	Q9GZR1-2
	SENP6	NM_001304792.2		c.52+8554C>T		intron	N/A	NP_001291721.1	F8W6D9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENP6	ENST00000447266.7	TSL:1 MANE Select	c.52+8554C>T		intron	N/A	ENSP00000402527.2	Q9GZR1-1
	SENP6	ENST00000370010.6	TSL:1	c.52+8554C>T		intron	N/A	ENSP00000359027.2	Q9GZR1-2
	SENP6	ENST00000938450.1		c.52+8554C>T		intron	N/A	ENSP00000608509.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46783 AN: 151834 Hom.: 7826 Cov.: 32

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: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.308 AC: 46806 AN: 151952 Hom.: 7827 Cov.: 32 AF XY: 0.312 AC XY: 23143 AN XY: 74286

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: 81 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16418 AN: 67932

Other (OTH) AF: 0.279 AC: 590 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.57
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs646967; hg19: chr6-76320846;