Variant 5-216797-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145265.3(CCDC127):c.53C>T(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCDC127
NM_145265.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

Variant links:

Genes affected

CCDC127 (HGNC:30520): (coiled-coil domain containing 127) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC127 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10654411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC127	NM_145265.3 linkuse as main transcript	c.53C>T	p.Ala18Val	missense_variant	2/3	ENST00000296824.4	NP_660308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCDC127	ENST00000296824.4 linkuse as main transcript	c.53C>T	p.Ala18Val	missense_variant	2/3	1	NM_145265.3	ENSP00000296824	P1
	ENST00000565521.1 linkuse as main transcript	n.87-105C>T		intron_variant, non_coding_transcript_variant		2
CCDC127	ENST00000441693.2 linkuse as main transcript	c.53C>T	p.Ala18Val	missense_variant	1/2	2		ENSP00000411206

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

150792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000439

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000330

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000376

AC:

AN:

239174

Hom.:

AF XY:

0.0000463

AC XY:

AN XY:

129684

show subpopulations

Gnomad AFR exome

AF:

0.000472

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000254

AC:

AN:

1457192

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

725194

show subpopulations

Gnomad4 AFR exome

AF:

0.000778

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000153

AC:

AN:

150792

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

73490

show subpopulations

Gnomad4 AFR

AF:

0.000439

Gnomad4 AMR

AF:

0.000330

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.53C>T (p.A18V) alteration is located in exon 2 (coding exon 1) of the CCDC127 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the alanine (A) at amino acid position 18 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

0.080

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

0.59

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.062

Sift

Benign

0.056

T;D

Sift4G

Benign

0.23

T;T

Polyphen

0.67

P;.

Vest4

0.19

MVP

0.68

MPC

2.0

ClinPred

0.043

GERP RS

4.6

Varity_R

0.069

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over