Variant chr4-7042755-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153376.3(CCDC96):c.184G>A(p.Ala62Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

CCDC96
NM_153376.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

CCDC96 (HGNC:26900): (cilia and flagella associated protein 184) Predicted to be involved in cilium assembly. Predicted to be active in axoneme and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

CCDC96 links:

(HGNC:):

links:

TADA2B (HGNC:30781): (transcriptional adaptor 2B) TADA2B functions as a transcriptional adaptor protein that potentiates transcription through coordination of histone acetyltransferase (HAT) activity and by linking activation factors to basal transcriptional machinery (Barlev et al., 2003 [PubMed 12972612]).[supplied by OMIM, Apr 2010]

TADA2B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10580033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC96	NM_153376.3 linkuse as main transcript	c.184G>A	p.Ala62Thr	missense_variant	1/1	ENST00000310085.6	NP_699207.1
LOC100129931	NR_033828.1 linkuse as main transcript	n.696+2225G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCDC96	ENST00000310085.6 linkuse as main transcript	c.184G>A	p.Ala62Thr	missense_variant	1/1		NM_153376.3	ENSP00000309285	P1
	ENST00000500031.1 linkuse as main transcript	n.696+2225G>A		intron_variant, non_coding_transcript_variant		2
TADA2B	ENST00000506692.1 linkuse as main transcript	c.-7+669C>T		intron_variant		2		ENSP00000422398

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.26e-7

AC:

AN:

1377220

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

679250

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.32e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.184G>A (p.A62T) alteration is located in exon 1 (coding exon 1) of the CCDC96 gene. This alteration results from a G to A substitution at nucleotide position 184, causing the alanine (A) at amino acid position 62 to be replaced by a threonine (T). 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

Benign

0.080

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.37

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.46

REVEL

Benign

0.051

Sift

Pathogenic

0.0

Sift4G

Benign

0.49

Polyphen

0.66

Vest4

0.12

MutPred

0.12

Gain of glycosylation at T61 (P = 0.0135);

MVP

0.030

ClinPred

0.42

GERP RS

2.4

Varity_R

0.097

gMVP

0.038

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