Variant 11-93370184-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_181645.4(DEUP1):c.544C>A(p.Gln182Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000754 in 1,326,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

DEUP1
NM_181645.4 missense, splice_region

Scores

Splicing: ADA: 0.9220

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Variant links:

Genes affected

DEUP1 (HGNC:26344): (deuterosome assembly protein 1) Enables identical protein binding activity. Predicted to be involved in centriole replication and de novo centriole assembly involved in multi-ciliated epithelial cell differentiation. Predicted to be located in cytoplasm. Predicted to be integral component of membrane. Predicted to be active in centriole and deuterosome. [provided by Alliance of Genome Resources, Apr 2022]

DEUP1 links:

DEUP1 (HGNC:):

DEUP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.35397074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEUP1	NM_181645.4 linkuse as main transcript	c.544C>A	p.Gln182Lys	missense_variant, splice_region_variant	6/14	ENST00000298050.9	NP_857596.2	Q05D60-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEUP1	ENST00000298050.9 linkuse as main transcript	c.544C>A	p.Gln182Lys	missense_variant, splice_region_variant	6/14	5	NM_181645.4	ENSP00000298050.3		Q05D60-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000463

AC:

AN:

216062

Hom.:

AF XY:

0.00000863

AC XY:

AN XY:

115808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000625

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1326368

Hom.:

Cov.:

AF XY:

0.00000753

AC XY:

AN XY:

664220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000242

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000517

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000100

Gnomad4 OTH exome

AF:

0.000107

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.544C>A (p.Q182K) alteration is located in exon 6 (coding exon 5) of the DEUP1 gene. This alteration results from a C to A substitution at nucleotide position 544, causing the glutamine (Q) at amino acid position 182 to be replaced by a lysine (K). 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

Benign

0.19

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

.;T;T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;.;M;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.9

D;N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Benign

0.079

T;D;T;D

Polyphen

1.0

.;.;D;.

Vest4

0.61, 0.70

MutPred

0.28

.;Gain of methylation at Q182 (P = 0.0091);Gain of methylation at Q182 (P = 0.0091);Gain of methylation at Q182 (P = 0.0091);

MVP

0.48

MPC

0.18

ClinPred

0.95

GERP RS

5.5

Varity_R

0.67

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.92

dbscSNV1_RF

Pathogenic

0.79

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