Variant chr22-46248230-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_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. 15/21 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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.174

Variant links:

Genes affected

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

CDPF1 links:

CDPF1 (HGNC:):

CDPF1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 2279547.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDPF1	NM_207327.5 linkuse as main transcript	c.55A>G	p.Thr19Ala	missense_variant	2/4	ENST00000314567.8	NP_997210.3	Q6NVV7
CDPF1	XM_011529960.3 linkuse as main transcript	c.55A>G	p.Thr19Ala	missense_variant	2/4		XP_011528262.1
CDPF1	XM_011529965.3 linkuse as main transcript	c.55A>G	p.Thr19Ala	missense_variant	2/4		XP_011528267.1	Q6NVV7
CDPF1	XM_047441165.1 linkuse as main transcript	c.55A>G	p.Thr19Ala	missense_variant	2/4		XP_047297121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDPF1	ENST00000314567.8 linkuse as main transcript	c.55A>G	p.Thr19Ala	missense_variant	2/4	1	NM_207327.5	ENSP00000325301.3		Q6NVV7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250684

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135574

show subpopulations

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 SAS 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:

AN:

1461542

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.7

DANN

Benign

0.69

DEOGEN2

Benign

0.0078

T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.27

T;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.6

.;N;.

PrimateAI

Benign

0.38

PROVEAN

Benign

0.82

N;N;N

REVEL

Benign

0.037

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.98

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.15

MutPred

0.29

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.030

MPC

0.16

ClinPred

0.025

GERP RS

-0.43

Varity_R

0.047

gMVP

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over