3-196885322-A-G

Variant names:

• chr3-196885322-A-G
• rs34707496
• NM_152699.5:c.141A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_152699.5(SENP5):​c.141A>G​(p.Pro47Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,614,208 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (21 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (36 hom.)
• Consequence: SENP5 NM_152699.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.109
• Publications: 3 publications found

Genes affected

SENP5 (HGNC:28407): (SUMO specific peptidase 5) The reversible posttranslational modification of proteins by the addition of small ubiquitin-like SUMO proteins (see SUMO1; MIM 601912) is required for numerous biologic processes. SUMO-specific proteases, such as SENP5, are responsible for the initial processing of SUMO precursors to generate a C-terminal diglycine motif required for the conjugation reaction. They also have isopeptidase activity for the removal of SUMO from high molecular mass SUMO conjugates (Di Bacco et al., 2006 [PubMed 16738315]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 3-196885322-A-G is Benign according to our data. Variant chr3-196885322-A-G is described in ClinVar as Benign. ClinVar VariationId is 787266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.109 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0109 (1666/152326) while in subpopulation AFR AF = 0.0319 (1326/41568). AF 95% confidence interval is 0.0305. There are 21 homozygotes in GnomAd4. There are 766 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1666 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152699.5. 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
	SENP5	NM_152699.5	MANE Select	c.141A>G	p.Pro47Pro	synonymous	Exon 2 of 10	NP_689912.2	Q96HI0-1
	SENP5	NM_001308045.2		c.141A>G	p.Pro47Pro	synonymous	Exon 2 of 9	NP_001294974.1	Q96HI0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SENP5	ENST00000323460.10	TSL:1 MANE Select	c.141A>G	p.Pro47Pro	synonymous	Exon 2 of 10	ENSP00000327197.5	Q96HI0-1
	SENP5	ENST00000875329.1		c.141A>G	p.Pro47Pro	synonymous	Exon 3 of 11	ENSP00000545388.1
	SENP5	ENST00000946893.1		c.141A>G	p.Pro47Pro	synonymous	Exon 3 of 11	ENSP00000616952.1

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1663 AN: 152208 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00220

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00414 AC: 1041 AN: 251362 AF XY: 0.00318

Gnomad AFR exome AF: 0.0321

Gnomad AMR exome AF: 0.00561

Gnomad ASJ exome AF: 0.00784

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00262 AC: 3828 AN: 1461882 Hom.: 36 Cov.: 32 AF XY: 0.00246 AC XY: 1786 AN XY: 727244

African (AFR) AF: 0.0314 AC: 1051 AN: 33480

American (AMR) AF: 0.00608 AC: 272 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00758 AC: 198 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.000168 AC: 9 AN: 53416

Middle Eastern (MID) AF: 0.00971 AC: 56 AN: 5768

European-Non Finnish (NFE) AF: 0.00170 AC: 1893 AN: 1112004

Other (OTH) AF: 0.00553 AC: 334 AN: 60396

GnomAD4 genome AF: 0.0109 AC: 1666 AN: 152326 Hom.: 21 Cov.: 32 AF XY: 0.0103 AC XY: 766 AN XY: 74492

African (AFR) AF: 0.0319 AC: 1326 AN: 41568

American (AMR) AF: 0.00870 AC: 133 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00221 AC: 150 AN: 68026

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.00690 Hom.: 6

Bravo AF: 0.0128

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00243

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.0
DANN	Benign	0.70
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism

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: rs34707496; hg19: chr3-196612193; COSMIC: COSV60207626;