NM_006324.3:c.425C>G

Variant names:

• chr16-75411930-G-C
• NM_006324.3:c.425C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006324.3(CFDP1):​c.425C>G​(p.Thr142Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CFDP1 NM_006324.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.363
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04894513).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006324.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFDP1	NM_006324.3	MANE Select	c.425C>G	p.Thr142Arg	missense	Exon 4 of 7	NP_006315.1	Q9UEE9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFDP1	ENST00000283882.4	TSL:1 MANE Select	c.425C>G	p.Thr142Arg	missense	Exon 4 of 7	ENSP00000283882.3	Q9UEE9-1
	CFDP1	ENST00000566901.5	TSL:1	n.534C>G		non_coding_transcript_exon	Exon 4 of 5
	CFDP1	ENST00000862206.1		c.425C>G	p.Thr142Arg	missense	Exon 4 of 8	ENSP00000532265.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.36
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.087
Sift	Benign	0.37	T
Sift4G	Benign	0.30	T
Polyphen		0.0020	B
Vest4		0.30
MutPred		0.27		Loss of phosphorylation at T142 (P = 0.0227)
MVP		0.43
MPC		0.013
ClinPred		0.044	T
GERP RS		-0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.031
gMVP		0.15

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

Other links and lift over

hg19: chr16-75445828; COSMIC: COSV99382758; COSMIC: COSV99382758;