22-46248263-G-C

Variant names:

• chr22-46248263-G-C
• rs547032323
• NM_207327.5:c.22C>G

Variant summary

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

The NM_207327.5(CDPF1):​c.22C>G​(p.Arg8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CDPF1 NM_207327.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 0 publications found

Genes affected

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

ENSG00000310243 (HGNC:):

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=0.058285117).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207327.5. 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
	CDPF1	NM_207327.5	MANE Select	c.22C>G	p.Arg8Gly	missense	Exon 2 of 4	NP_997210.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDPF1	ENST00000314567.8	TSL:1 MANE Select	c.22C>G	p.Arg8Gly	missense	Exon 2 of 4	ENSP00000325301.3	Q6NVV7
	CDPF1	ENST00000381037.4	TSL:1	n.22C>G		non_coding_transcript_exon	Exon 2 of 5	ENSP00000370425.4	H9KV78
	CDPF1	ENST00000904360.1		c.22C>G	p.Arg8Gly	missense	Exon 3 of 5	ENSP00000574419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460832 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726698

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111468

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.2
DANN	Benign	0.96
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.037
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.096
Sift	Benign	0.14	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.31		Loss of sheet (P = 0.0126)
MVP		0.067
MPC		0.21
ClinPred		0.090	T
GERP RS		0.027
PromoterAI		-0.024	Neutral
Varity_R		0.11
gMVP		0.20
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs547032323; hg19: chr22-46644160;