5-205323-C-G

Variant names:

• chr5-205323-C-G
• rs1734148809
• NM_145265.3:c.757G>C

Variant summary

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

The NM_145265.3(CCDC127):​c.757G>C​(p.Val253Leu) 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. 16/21 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: CCDC127 NM_145265.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58

Genes affected

CCDC127 (HGNC:30520): (coiled-coil domain containing 127) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12768209).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC127	NM_145265.3	c.757G>C	p.Val253Leu	missense_variant	Exon 3 of 3	ENST00000296824.4	NP_660308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC127	ENST00000296824.4	c.757G>C	p.Val253Leu	missense_variant	Exon 3 of 3	1	NM_145265.3	ENSP00000296824.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.757G>C (p.V253L) alteration is located in exon 3 (coding exon 2) of the CCDC127 gene. This alteration results from a G to C substitution at nucleotide position 757, causing the valine (V) at amino acid position 253 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	0.24
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.77
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.26
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Polyphen		0.0030	B
Vest4		0.10
MutPred		0.29		Loss of methylation at K248 (P = 0.1008);
MVP		0.43
MPC		0.19
ClinPred		0.080	T
GERP RS		2.7
Varity_R		0.060
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1734148809; hg19: chr5-205438;