17-16342702-A-C

Variant names:

• chr17-16342702-A-C
• rs7477
• NM_181716.3:c.*115T>G

Variant summary

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

The NM_181716.3(CENPV):​c.*115T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,256,326 control chromosomes in the GnomAD database, including 135,929 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 0.37 (12736 hom., cov: 31)
  • Exomes 𝑓: 0.46 (123193 hom.)
• Consequence: CENPV NM_181716.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 37 publications found

Genes affected

CENPV (HGNC:29920): (centromere protein V) Predicted to enable carbon-sulfur lyase activity and metal ion binding activity. Involved in pericentric heterochromatin assembly; positive regulation of cytokinesis; and regulation of chromosome organization. Acts upstream of or within ameboidal-type cell migration. Located in several cellular components, including midbody; nucleus; and spindle midzone. [provided by Alliance of Genome Resources, Apr 2022]

PIGL (HGNC:8966): (phosphatidylinositol glycan anchor biosynthesis class L) This gene encodes an enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI). Study of a similar rat enzyme suggests that this protein localizes to the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

PIGL Gene-Disease associations (from GenCC):

• CHIME syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet, PanelApp Australia
• syndromic intellectual disability

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hyperphosphatasia-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPV	NM_181716.3	c.*115T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000299736.5	NP_859067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPV	ENST00000299736.5	c.*115T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_181716.3	ENSP00000299736.4

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56859 AN: 151802 Hom.: 12738 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.398

GnomAD4 exome AF: 0.455 AC: 502847 AN: 1104406 Hom.: 123193 Cov.: 14 AF XY: 0.453 AC XY: 252664 AN XY: 557706

African (AFR) AF: 0.153 AC: 4002 AN: 26074

American (AMR) AF: 0.297 AC: 11404 AN: 38366

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 11350 AN: 20938

East Asian (EAS) AF: 0.00119 AC: 45 AN: 37820

South Asian (SAS) AF: 0.293 AC: 20962 AN: 71476

European-Finnish (FIN) AF: 0.489 AC: 22413 AN: 45842

Middle Eastern (MID) AF: 0.501 AC: 1830 AN: 3656

European-Non Finnish (NFE) AF: 0.505 AC: 409803 AN: 812200

Other (OTH) AF: 0.438 AC: 21038 AN: 48034

GnomAD4 genome AF: 0.374 AC: 56866 AN: 151920 Hom.: 12736 Cov.: 31 AF XY: 0.371 AC XY: 27523 AN XY: 74210

African (AFR) AF: 0.163 AC: 6781 AN: 41486

American (AMR) AF: 0.380 AC: 5785 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1920 AN: 3470

East Asian (EAS) AF: 0.00541 AC: 28 AN: 5180

South Asian (SAS) AF: 0.274 AC: 1319 AN: 4808

European-Finnish (FIN) AF: 0.502 AC: 5271 AN: 10508

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34324 AN: 67922

Other (OTH) AF: 0.400 AC: 840 AN: 2100

Alfa AF: 0.447 Hom.: 34468

Bravo AF: 0.355

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.50
PhyloP100		0.048
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7477; hg19: chr17-16246016; COSMIC: COSV55333333; COSMIC: COSV55333333;