NM_015439.3:c.-134C>G

Variant names:

• chr6-138773811-C-G
• rs770947119
• NM_015439.3:c.-134C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015439.3(CCDC28A):​c.-134C>G variant causes a 5 prime UTR 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: 32)
• Consequence: CCDC28A NM_015439.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.18
• Publications: 0 publications found

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-AS1 (HGNC:51715): (CCDC28A antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044190586).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015439.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC28A	NM_015439.3	MANE Select	c.-134C>G		5_prime_UTR	Exon 1 of 6	NP_056254.2	B4DUJ5
	CCDC28A	NM_001379071.1		c.-134C>G		5_prime_UTR	Exon 1 of 4	NP_001366000.1
	CCDC28A-AS1	NR_161203.1		n.-108G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC28A	ENST00000617445.5	TSL:1 MANE Select	c.-134C>G		5_prime_UTR	Exon 1 of 6	ENSP00000482946.1	B4DUJ5
	CCDC28A	ENST00000864347.1		c.-134C>G		5_prime_UTR	Exon 1 of 6	ENSP00000534406.1
	CCDC28A	ENST00000864346.1		c.-43+270C>G		intron	N/A	ENSP00000534405.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.5
DANN	Benign	0.61
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
PhyloP100		-2.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.0060
Sift	Benign	0.14	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.26		Gain of glycosylation at T46 (P = 0.0252)
MVP		0.12
MPC		0.19
ClinPred		0.70	D
GERP RS		-9.9
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.036
gMVP		0.023

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

Other links and lift over

dbSNP: rs770947119; hg19: chr6-139094948;