Variant 6-138776181-G-A 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_015439.3(CCDC28A):c.61G>A(p.Val21Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC28A
NM_015439.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.02

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:

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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=0.07853797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC28A	NM_015439.3 linkuse as main transcript	c.61G>A	p.Val21Ile	missense_variant	2/6	ENST00000617445.5	NP_056254.2
CCDC28A	NM_001379071.1 linkuse as main transcript	c.61G>A	p.Val21Ile	missense_variant	2/4		NP_001366000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC28A	ENST00000617445.5 linkuse as main transcript	c.61G>A	p.Val21Ile	missense_variant	2/6	1	NM_015439.3	ENSP00000482946	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251468

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135906

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727200

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Myoepithelial tumor

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine

Nov 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0034

T;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.087

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.64

T;.;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.46

N;N;.

MutationTaster

Benign

0.97

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.47

.;N;.

REVEL

Benign

0.034

Sift

Benign

0.13

.;T;.

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.13

MutPred

0.29

Loss of ubiquitination at K116 (P = 0.1576);Loss of ubiquitination at K116 (P = 0.1576);.;

MVP

0.40

MPC

0.17

ClinPred

0.18

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.077

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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