Genetic Variant CENATAC:p.Glu72Val (chr11-118998524-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198489.3(CENATAC):c.215A>T(p.Glu72Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000865 in 1,607,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

CENATAC
NM_198489.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

Variant links:

Genes affected

CENATAC (HGNC:30460): (centrosomal AT-AC splicing factor) This gene encodes a protein thought to contain a coiled coil motif. No function has been determined for the encoded protein. A pseudogene of this gene is located on chromosome 20. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

CENATAC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENATAC	NM_198489.3 link	c.215A>T	p.Glu72Val	missense_variant	Exon 2 of 11	ENST00000334418.6	NP_940891.1	Q86UT8
CENATAC	NR_104049.2 link	n.275A>T		non_coding_transcript_exon_variant	Exon 2 of 11
CENATAC	NR_104050.2 link	n.275A>T		non_coding_transcript_exon_variant	Exon 2 of 11
CENATAC	NR_104051.2 link	n.275A>T		non_coding_transcript_exon_variant	Exon 2 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENATAC	ENST00000334418.6 link	c.215A>T	p.Glu72Val	missense_variant	Exon 2 of 11	1	NM_198489.3	ENSP00000334767.1		Q86UT8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

235042

Hom.:

AF XY:

0.00000784

AC XY:

AN XY:

127510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000948

AC:

138

AN:

1455110

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

723300

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.215A>T (p.E72V) alteration is located in exon 2 (coding exon 2) of the CCDC84 gene. This alteration results from a A to T substitution at nucleotide position 215, causing the glutamic acid (E) at amino acid position 72 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.57

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.27

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0070

Polyphen

0.80

Vest4

0.79

MutPred

0.54

Loss of solvent accessibility (P = 0.0703);

MVP

0.65

MPC

0.43

ClinPred

0.97

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.56

gMVP

0.64

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over