3-107378254-C-G

Variant names:

• chr3-107378254-C-G
• rs762728121
• NM_032600.3:c.667C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032600.3(CCDC54):​c.667C>G​(p.Arg223Gly) 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 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R223C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC54 NM_032600.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

Genes affected

CCDC54 (HGNC:30703): (coiled-coil domain containing 54)

CCDC54-AS1 (HGNC:56107): (CCDC54 antisense RNA 1)

DUBR (HGNC:48569): (DPPA2 upstream binding RNA) Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II; positive regulation of myoblast differentiation; and regulation of DNA methylation. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032600.3. 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
	CCDC54	NM_032600.3	MANE Select	c.667C>G	p.Arg223Gly	missense	Exon 1 of 1	NP_115989.1	Q8NEL0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC54	ENST00000261058.3	TSL:6 MANE Select	c.667C>G	p.Arg223Gly	missense	Exon 1 of 1	ENSP00000261058.1	Q8NEL0
	CCDC54-AS1	ENST00000593837.1	TSL:5	n.23+2331G>C		intron	N/A
	CCDC54-AS1	ENST00000595232.2	TSL:5	n.488+2331G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461696 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727162

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	21
DANN	Benign	0.78
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.036
Sift	Benign	0.17	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.087
MutPred		0.19		Loss of MoRF binding (P = 0.0432)
MVP		0.030
MPC		0.044
ClinPred		0.050	T
GERP RS		1.1
Varity_R		0.074
gMVP		0.060
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.42		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs762728121; hg19: chr3-107097101;