rs148239448

Variant names:

• chr5-69307992-C-G
• rs148239448
• NM_176816.5:c.490G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-69307992-C-G
• chr5-69307992-C-T

Variant summary

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

The NM_176816.5(CCDC125):​c.490G>C​(p.Val164Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC125 NM_176816.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

Genes affected

CCDC125 (HGNC:28924): (coiled-coil domain containing 125) Enables identical protein binding activity. Involved in activation of GTPase activity; negative regulation of Rho protein signal transduction; and negative regulation of cell motility. Located in cytoplasm. [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=0.14847049).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC125	NM_176816.5	c.490G>C	p.Val164Leu	missense_variant	Exon 5 of 12	ENST00000396496.7	NP_789786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC125	ENST00000396496.7	c.490G>C	p.Val164Leu	missense_variant	Exon 5 of 12	5	NM_176816.5	ENSP00000379754.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.0015	T;T;T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.60	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.62	N;N;N;N
REVEL	Benign	0.027
Sift	Benign	0.36	T;T;T;T
Sift4G	Benign	0.62	T;T;T;T
Polyphen		0.33	B;B;.;B
Vest4		0.28
MutPred		0.35		Gain of disorder (P = 0.0685);Gain of disorder (P = 0.0685);.;.;
MVP		0.099
MPC		0.070
ClinPred		0.19	T
GERP RS		2.4
Varity_R		0.041
gMVP		0.053

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: rs148239448; hg19: chr5-68603819;