chr5-69281640-T-C

Position:

• chr5-69281640-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176816.5(CCDC125):​c.*1089A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,078 control chromosomes in the GnomAD database, including 3,581 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (3581 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC125 NM_176816.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC125	NM_176816.5	c.*1089A>G		3_prime_UTR_variant	12/12	ENST00000396496.7	NP_789786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC125	ENST00000396496.7	c.*1089A>G		3_prime_UTR_variant	12/12	5	NM_176816.5	ENSP00000379754	P1
CCDC125	ENST00000396499.5	c.*1089A>G		3_prime_UTR_variant	11/11	1		ENSP00000379756	P1
CCDC125	ENST00000460090.5	n.1978A>G		non_coding_transcript_exon_variant	6/6	1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25885 AN: 151960 Hom.: 3565 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.0711

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.147

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.171 AC: 25937 AN: 152078 Hom.: 3581 Cov.: 32 AF XY: 0.170 AC XY: 12604 AN XY: 74358

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.0708

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.0416

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.145

Alfa AF: 0.0911 Hom.: 1636

Bravo AF: 0.185

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.6
DANN	Benign	0.87

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

LitVar

Other links and lift over

dbSNP: rs12651858; hg19: chr5-68577467;