4-7041893-C-G

Position:

• chr4-7041893-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153376.3(CCDC96):​c.1046G>C​(p.Gly349Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC96 NM_153376.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.740

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]

(HGNC:):

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]

ACMG classification

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=0.18371227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC96	NM_153376.3	c.1046G>C	p.Gly349Ala	missense_variant	1/1	ENST00000310085.6	NP_699207.1
LOC100129931	NR_033828.1	n.696+3087G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC96	ENST00000310085.6	c.1046G>C	p.Gly349Ala	missense_variant	1/1		NM_153376.3	ENSP00000309285	P1
	ENST00000500031.1	n.696+3087G>C		intron_variant, non_coding_transcript_variant		2
TADA2B	ENST00000506692.1			upstream_gene_variant		2		ENSP00000422398

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.1046G>C (p.G349A) alteration is located in exon 1 (coding exon 1) of the CCDC96 gene. This alteration results from a G to C substitution at nucleotide position 1046, causing the glycine (G) at amino acid position 349 to be replaced by an alanine (A). 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	0.28
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Benign	0.046	D
Sift4G	Benign	0.52	T
Polyphen		0.91	P
Vest4		0.40
MutPred		0.47		Gain of glycosylation at S344 (P = 0.0374);
MVP		0.22
ClinPred		0.50	D
GERP RS		4.0
Varity_R		0.13
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-7043620;