22-46248230-T-A

Variant names:

• chr22-46248230-T-A
• rs1232967321
• NM_207327.5:c.55A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207327.5(CDPF1):​c.55A>T​(p.Thr19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 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. T19A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: CDPF1 NM_207327.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 0 publications found

Genes affected

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

ENSG00000310243 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.55A>T	p.Thr19Ser	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.55A>T	p.Thr19Ser	missense	Exon 2 of 4	ENSP00000325301.3	Q6NVV7
	CDPF1	ENST00000381037.4	TSL:1	n.55A>T		non_coding_transcript_exon	Exon 2 of 5	ENSP00000370425.4	H9KV78
	CDPF1	ENST00000904360.1		c.55A>T	p.Thr19Ser	missense	Exon 3 of 5	ENSP00000574419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461542 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 727054

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111884

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.17
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.012
Sift	Benign	0.51	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.30		Loss of sheet (P = 0.0817)
MVP		0.061
MPC		0.15
ClinPred		0.037	T
GERP RS		-0.43
PromoterAI		-0.0090	Neutral
Varity_R		0.054
gMVP		0.096
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: -10

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1232967321; hg19: chr22-46644127;