rs770947119

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-138773811-C-G
• chr6-138773811-C-T

Variant summary

Our verdict is Likely benign. Variant got -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

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=0.044190586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC28A	NM_015439.3	c.-134C>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000617445.5	NP_056254.2
CCDC28A	NM_001379071.1	c.-134C>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.-134C>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_015439.3	ENSP00000482946.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.137C>G (p.T46S) alteration is located in exon 1 (coding exon 1) of the CCDC28A gene. This alteration results from a C to G substitution at nucleotide position 137, causing the threonine (T) at amino acid position 46 to be replaced by a serine (S). 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	0.090
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.5
DANN	Benign	0.61
DEOGEN2	Benign	0.0012	T;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;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.12	.;N
REVEL	Benign	0.0060
Sift	Benign	0.14	.;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.26		Gain of glycosylation at T46 (P = 0.0252);Gain of glycosylation at T46 (P = 0.0252);
MVP		0.12
MPC		0.19
ClinPred		0.70	D
GERP RS		-9.9
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

Publications

LitVar

Other links and lift over

dbSNP: rs770947119; hg19: chr6-139094948;