chr5-69306867-A-T

Variant names:

• chr5-69306867-A-T
• NM_176816.5:c.567T>A

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.567T>A​(p.Asp189Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC125 NM_176816.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81
• Publications: 0 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=0.2616244).

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.567T>A	p.Asp189Glu	missense	Exon 6 of 12	NP_789786.2	Q86Z20-1
	CCDC125	NM_001297697.2		c.192T>A	p.Asp64Glu	missense	Exon 7 of 13	NP_001284626.1	Q86Z20-2
	CCDC125	NM_001297696.2		c.564T>A	p.Asp188Glu	missense	Exon 6 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.567T>A	p.Asp189Glu	missense	Exon 6 of 12	ENSP00000379754.2	Q86Z20-1
	CCDC125	ENST00000396499.5	TSL:1	c.567T>A	p.Asp189Glu	missense	Exon 5 of 11	ENSP00000379756.1	Q86Z20-1
	CCDC125	ENST00000460090.5	TSL:1	n.229-6740T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.24
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.32		Gain of disorder (P = 0.1272)
MVP		0.095
MPC		0.38
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.23
gMVP		0.14
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

hg19: chr5-68602694;