22-46248175-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_207327.5(CDPF1):c.110T>G(p.Met37Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDPF1 NM_207327.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45

Genes affected

CDPF1 (HGNC:33710): (cysteine rich DPF motif domain containing 1)

ACMG classification

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=0.38683042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDPF1	NM_207327.5	c.110T>G	p.Met37Arg	missense_variant	2/4	ENST00000314567.8
CDPF1	XM_011529960.3	c.110T>G	p.Met37Arg	missense_variant	2/4
CDPF1	XM_011529965.3	c.110T>G	p.Met37Arg	missense_variant	2/4
CDPF1	XM_047441165.1	c.110T>G	p.Met37Arg	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDPF1	ENST00000314567.8	c.110T>G	p.Met37Arg	missense_variant	2/4	1	NM_207327.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.110T>G (p.M37R) alteration is located in exon 2 (coding exon 1) of the CDPF1 gene. This alteration results from a T to G substitution at nucleotide position 110, causing the methionine (M) at amino acid position 37 to be replaced by an arginine (R). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.079	T;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.62	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.090	B;B;B
Vest4		0.67
MutPred		0.35		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.18
MPC		0.25
ClinPred		0.84	D
GERP RS		5.4
Varity_R		0.87
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-46644072;