NM_176816.5:c.1274G>A

Variant names:

• chr5-69282991-C-T
• NM_176816.5:c.1274G>A

Variant summary

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

The NM_176816.5(CCDC125):​c.1274G>A​(p.Ser425Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,454,314 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC125 NM_176816.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC125	NM_176816.5	c.1274G>A	p.Ser425Asn	missense_variant	Exon 12 of 12	ENST00000396496.7	NP_789786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC125	ENST00000396496.7	c.1274G>A	p.Ser425Asn	missense_variant	Exon 12 of 12	5	NM_176816.5	ENSP00000379754.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454314 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722850

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.7	M;M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.5	N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0090	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.69
MutPred		0.39		Loss of phosphorylation at S425 (P = 0.0266);Loss of phosphorylation at S425 (P = 0.0266);.;
MVP		0.37
MPC		0.35
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.51
gMVP		0.34

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: chr5-68578818;