chr1-3752683-G-C

Position:

• chr1-3752683-G-C

Variant summary

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

The NM_152492.3(CCDC27):​c.202G>C​(p.Val68Leu) variant causes a missense 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. 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)
• Consequence: CCDC27 NM_152492.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.79

Genes affected

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

CCDC27 (HGNC:):

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=0.032336533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC27	NM_152492.3	c.202G>C	p.Val68Leu	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.202G>C	p.Val68Leu	missense_variant	1/12	1	NM_152492.3	ENSP00000294600.2
CCDC27	ENST00000462521.2	n.202G>C		non_coding_transcript_exon_variant	1/12	5		ENSP00000463275.1
CCDC27	ENST00000636250.1	n.712G>C		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Jan 03, 2024

The c.202G>C (p.V68L) alteration is located in exon 1 (coding exon 1) of the CCDC27 gene. This alteration results from a G to C substitution at nucleotide position 202, causing the valine (V) at amino acid position 68 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0030
DANN	Benign	0.46
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.021
Sift	Benign	0.30	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.085
MutPred		0.35		Loss of MoRF binding (P = 0.1576);
MVP		0.030
MPC		0.13
ClinPred		0.22	T
GERP RS		-7.4
Varity_R		0.038
gMVP		0.036

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-3669247;