Variant chr6-138779940-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015439.3(CCDC28A):c.277C>A(p.Leu93Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000328 in 1,461,202 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

CCDC28A
NM_015439.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Variant links:

Genes affected

CCDC28A (HGNC:21098): (coiled-coil domain containing 28A) This gene encodes a coiled-coil domain containing protein. Although the specific function of this gene has not yet been determined, this gene is a known translocation partner of nucleoporin 98 in acute leukemias. The resulting fusion gene produces a nucleoporin 98-coiled-coil domain-containing protein 28A chimeric protein which may be involved in promoting myeloproliferative neoplasms. [provided by RefSeq, Jan 2017]

CCDC28A 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
CCDC28A	NM_015439.3 link	c.277C>A	p.Leu93Ile	missense_variant	Exon 3 of 6	ENST00000617445.5	NP_056254.2
CCDC28A	NM_001379071.1 link	c.277C>A	p.Leu93Ile	missense_variant	Exon 3 of 4		NP_001366000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC28A	ENST00000617445.5 link	c.277C>A	p.Leu93Ile	missense_variant	Exon 3 of 6	1	NM_015439.3	ENSP00000482946.1		B4DUJ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250864

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135604

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461202

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726932

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:

0.0000432

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.547C>A (p.L183I) alteration is located in exon 3 (coding exon 3) of the CCDC28A gene. This alteration results from a C to A substitution at nucleotide position 547, causing the leucine (L) at amino acid position 183 to be replaced by an isoleucine (I). 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

0.54

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

T;T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

D;.;D

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

M;M;.

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.7

.;N;.

REVEL

Benign

0.25

Sift

Uncertain

0.021

.;D;.

Sift4G

Benign

0.098

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.70

MutPred

0.46

Loss of disorder (P = 0.1197);Loss of disorder (P = 0.1197);.;

MVP

0.55

MPC

0.83

ClinPred

0.88

GERP RS

4.2

Varity_R

0.26

gMVP

0.42

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