NM_176816.5:c.814G>A

Variant names:

• chr5-69300014-C-T
• rs755608900
• NM_176816.5:c.814G>A

Variant summary

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

The NM_176816.5(CCDC125):​c.814G>A​(p.Glu272Lys) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC125 NM_176816.5 missense, splice_region
• Scores: Splicing: ADA: 0.7965
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26

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.814G>A	p.Glu272Lys	missense_variant, splice_region_variant	Exon 8 of 12	ENST00000396496.7	NP_789786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC125	ENST00000396496.7	c.814G>A	p.Glu272Lys	missense_variant, splice_region_variant	Exon 8 of 12	5	NM_176816.5	ENSP00000379754.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251438 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135888

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459868 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726420

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.7	M;M;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.0	D;D;N;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.030	D;D;D;D
Polyphen		0.95	P;P;.;P
Vest4		0.89
MutPred		0.45		Gain of ubiquitination at E272 (P = 0.0162);Gain of ubiquitination at E272 (P = 0.0162);.;.;
MVP		0.37
MPC		0.073
ClinPred		0.91	D
GERP RS		4.7
Varity_R		0.59
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.80
dbscSNV1_RF	Pathogenic	0.79
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

LitVar

Other links and lift over

dbSNP: rs755608900; hg19: chr5-68595841;