6-138773832-C-G

Variant names:

• chr6-138773832-C-G
• rs752013826
• NM_015439.3:c.-113C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015439.3(CCDC28A):​c.-113C>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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC28A NM_015439.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046158552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC28A	NM_015439.3	c.-113C>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000617445.5	NP_056254.2
CCDC28A	NM_001379071.1	c.-113C>G		5_prime_UTR_variant	Exon 1 of 4		NP_001366000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC28A	ENST00000617445	c.-113C>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_015439.3	ENSP00000482946.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461678 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727134

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.000206 AC: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.0051	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.44	T;.
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.046	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.27	.;N
REVEL	Benign	0.019
Sift	Uncertain	0.017	.;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.0010	B;B
Vest4		0.28
MVP		0.11
MPC		0.31
ClinPred		0.051	T
GERP RS		-1.9
Varity_R		0.065
gMVP		0.033

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

Other links and lift over

dbSNP: rs752013826; hg19: chr6-139094969;