1-3752794-A-G

Position:

• chr1-3752794-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152492.3(CCDC27):​c.313A>G​(p.Lys105Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CCDC27 NM_152492.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

Genes affected

CCDC27 (HGNC:26546): (coiled-coil domain containing 27)

CCDC27 (HGNC:):

ACMG classification

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=0.1465663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC27	NM_152492.3	c.313A>G	p.Lys105Glu	missense_variant	1/12	ENST00000294600.7	NP_689705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC27	ENST00000294600.7	c.313A>G	p.Lys105Glu	missense_variant	1/12	1	NM_152492.3	ENSP00000294600.2
CCDC27	ENST00000462521.2	n.313A>G		non_coding_transcript_exon_variant	1/12	5		ENSP00000463275.1
CCDC27	ENST00000636250.1	n.823A>G		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459122 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725452

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.313A>G (p.K105E) alteration is located in exon 1 (coding exon 1) of the CCDC27 gene. This alteration results from a A to G substitution at nucleotide position 313, causing the lysine (K) at amino acid position 105 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Benign	0.51
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.076
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.020	D
Polyphen		0.87	P
Vest4		0.35
MutPred		0.14		Loss of MoRF binding (P = 0.0054);
MVP		0.25
MPC		0.56
ClinPred		0.38	T
GERP RS		1.5
Varity_R		0.092
gMVP		0.080

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs776622907; hg19: chr1-3669358;