Genetic Variant CFDP1:p.Glu112Gln (chr16-75412603-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006324.3(CFDP1):c.334G>C(p.Glu112Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

CFDP1
NM_006324.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

Variant links:

Genes affected

CFDP1 (HGNC:1873): (craniofacial development protein 1) Predicted to act upstream of or within several processes, including cell adhesion; negative regulation of fibroblast apoptotic process; and regulation of cell shape. Predicted to be located in kinetochore. [provided by Alliance of Genome Resources, Apr 2022]

CFDP1 links:

ENSG00000261717 (HGNC:):

ENSG00000261717 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37585467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFDP1	NM_006324.3 link	c.334G>C	p.Glu112Gln	missense_variant	Exon 3 of 7	ENST00000283882.4	NP_006315.1	Q9UEE9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFDP1	ENST00000283882.4 link	c.334G>C	p.Glu112Gln	missense_variant	Exon 3 of 7	1	NM_006324.3	ENSP00000283882.3		Q9UEE9-1
ENSG00000261717	ENST00000567194.5 link	c.*81G>C		downstream_gene_variant		2		ENSP00000457654.1		H3BUI4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.334G>C (p.E112Q) alteration is located in exon 3 (coding exon 3) of the CFDP1 gene. This alteration results from a G to C substitution at nucleotide position 334, causing the glutamic acid (E) at amino acid position 112 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.013

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.1

REVEL

Benign

0.15

Sift

Benign

0.19

Sift4G

Benign

0.44

Polyphen

0.98

Vest4

0.33

MutPred

0.19

Gain of MoRF binding (P = 0.0214);

MVP

0.75

MPC

0.048

ClinPred

0.76

GERP RS

6.1

Varity_R

0.14

gMVP

0.12

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