1-32204309-T-C

Variant names:

• chr1-32204309-T-C
• NM_024296.5:c.455T>C

Variant summary

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

The NM_024296.5(CCDC28B):​c.455T>C​(p.Val152Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC28B NM_024296.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02

Genes affected

CCDC28B (HGNC:28163): (coiled-coil domain containing 28B) The product of this gene localizes to centrosomes and basal bodies. The protein colocalizes with several proteins associated with Bardet-Biedl syndrome (BBS) and participates in the regulation of cilia development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

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=0.07239133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC28B	NM_024296.5	c.455T>C	p.Val152Ala	missense_variant	Exon 4 of 6	ENST00000373602.10	NP_077272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC28B	ENST00000373602.10	c.455T>C	p.Val152Ala	missense_variant	Exon 4 of 6	1	NM_024296.5	ENSP00000362704.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.455T>C (p.V152A) alteration is located in exon 4 (coding exon 3) of the CCDC28B gene. This alteration results from a T to C substitution at nucleotide position 455, causing the valine (V) at amino acid position 152 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	0.085
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.041	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.12
Sift	Benign	0.35	T;T
Sift4G	Uncertain	0.030	D;D
Polyphen		0.0	B;.
Vest4		0.15
MutPred		0.15		Loss of stability (P = 0.1003);Loss of stability (P = 0.1003);
MVP		0.14
MPC		0.38
ClinPred		0.075	T
GERP RS		3.7
Varity_R		0.027
gMVP		0.046

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-32669910;