chr5-160428637-C-T

Variant names:

• chr5-160428637-C-T
• rs7335
• NM_004219.4:c.565C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004219.4(PTTG1):​c.565C>T​(p.Leu189Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 1,614,014 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (105 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (104 hom.)
• Consequence: PTTG1 NM_004219.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.425
• Publications: 2 publications found

Genes affected

PTTG1 (HGNC:9690): (PTTG1 regulator of sister chromatid separation, securin) The encoded protein is a homolog of yeast securin proteins, which prevent separins from promoting sister chromatid separation. It is an anaphase-promoting complex (APC) substrate that associates with a separin until activation of the APC. The gene product has transforming activity in vitro and tumorigenic activity in vivo, and the gene is highly expressed in various tumors. The gene product contains 2 PXXP motifs, which are required for its transforming and tumorigenic activities, as well as for its stimulation of basic fibroblast growth factor expression. It also contains a destruction box (D box) that is required for its degradation by the APC. The acidic C-terminal region of the encoded protein can act as a transactivation domain. The gene product is mainly a cytosolic protein, although it partially localizes in the nucleus. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 5-160428637-C-T is Benign according to our data. Variant chr5-160428637-C-T is described in ClinVar as Benign. ClinVar VariationId is 790985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.425 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004219.4. 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
	PTTG1	NM_004219.4	MANE Select	c.565C>T	p.Leu189Leu	synonymous	Exon 6 of 6	NP_004210.1	Q6IAL9
	PTTG1	NM_001282382.1		c.565C>T	p.Leu189Leu	synonymous	Exon 5 of 5	NP_001269311.1	Q6IAL9
	PTTG1	NM_001282383.1		c.565C>T	p.Leu189Leu	synonymous	Exon 6 of 6	NP_001269312.1	O95997

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTTG1	ENST00000352433.10	TSL:1 MANE Select	c.565C>T	p.Leu189Leu	synonymous	Exon 6 of 6	ENSP00000344936.5	O95997
	PTTG1	ENST00000393964.1	TSL:1	c.565C>T	p.Leu189Leu	synonymous	Exon 5 of 5	ENSP00000377536.1	O95997
	PTTG1	ENST00000922255.1		c.610C>T	p.Leu204Leu	synonymous	Exon 6 of 6	ENSP00000592314.1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3041 AN: 152174 Hom.: 105 Cov.: 33

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00739

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00530 AC: 1332 AN: 251430 AF XY: 0.00392

Gnomad AFR exome AF: 0.0717

Gnomad AMR exome AF: 0.00370

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00209 AC: 3056 AN: 1461722 Hom.: 104 Cov.: 30 AF XY: 0.00182 AC XY: 1327 AN XY: 727170

African (AFR) AF: 0.0749 AC: 2506 AN: 33462

American (AMR) AF: 0.00411 AC: 184 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39680

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1111914

Other (OTH) AF: 0.00442 AC: 267 AN: 60386

GnomAD4 genome AF: 0.0200 AC: 3044 AN: 152292 Hom.: 105 Cov.: 33 AF XY: 0.0190 AC XY: 1412 AN XY: 74466

African (AFR) AF: 0.0699 AC: 2902 AN: 41528

American (AMR) AF: 0.00738 AC: 113 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68036

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.0112 Hom.: 26

Bravo AF: 0.0226

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.5
DANN	Benign	0.74
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7335; hg19: chr5-159855644;