22-46248230-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_207327.5(CDPF1):​c.55A>G​(p.Thr19Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,542 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CDPF1 NM_207327.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.019292414).
• BP6: Variant 22-46248230-T-C is Benign according to our data. Variant chr22-46248230-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2279547.Status of the report is criteria_provided_single_submitter, 1 stars.

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>G	p.Thr19Ala	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>G	p.Thr19Ala	missense	Exon 2 of 4	ENSP00000325301.3	Q6NVV7
	CDPF1	ENST00000381037.4	TSL:1	n.55A>G		non_coding_transcript_exon	Exon 2 of 5	ENSP00000370425.4	H9KV78
	CDPF1	ENST00000904360.1		c.55A>G	p.Thr19Ala	missense	Exon 3 of 5	ENSP00000574419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250684 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461542 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 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: 0.00000270 AC: 3 AN: 1111884

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.050
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.7
DANN	Benign	0.69
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.6	N
PhyloP100		0.17
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.82	N
REVEL	Benign	0.037
Sift	Benign	1.0	T
Sift4G	Benign	0.98	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.29		Loss of sheet (P = 0.0457)
MVP		0.030
MPC		0.16
ClinPred		0.025	T
GERP RS		-0.43
PromoterAI		-0.0049	Neutral
Varity_R		0.047
gMVP		0.12
Mutation Taster		=90/10	polymorphism

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

dbSNP: rs1232967321; hg19: chr22-46644127; COSMIC: COSV53078631; COSMIC: COSV53078631;