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. The variant received 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. 15/22 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. V164M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC125 NM_176816.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14847049).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176816.5. 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
	CCDC125	NM_176816.5	MANE Select	c.490G>C	p.Val164Leu	missense	Exon 5 of 12	NP_789786.2	Q86Z20-1
	CCDC125	NM_001297697.2		c.115G>C	p.Val39Leu	missense	Exon 6 of 13	NP_001284626.1	Q86Z20-2
	CCDC125	NM_001297696.2		c.487G>C	p.Val163Leu	missense	Exon 5 of 11	NP_001284625.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC125	ENST00000396496.7	TSL:5 MANE Select	c.490G>C	p.Val164Leu	missense	Exon 5 of 12	ENSP00000379754.2	Q86Z20-1
	CCDC125	ENST00000396499.5	TSL:1	c.490G>C	p.Val164Leu	missense	Exon 4 of 11	ENSP00000379756.1	Q86Z20-1
	CCDC125	ENST00000460090.5	TSL:1	n.229-7865G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.28
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.027
Sift	Benign	0.36	T
Sift4G	Benign	0.62	T
Polyphen		0.33	B
Vest4		0.28
MutPred		0.35		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
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs148239448; hg19: chr5-68603819;