Variant 11-694968-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000382409.4(DEAF1):c.80C>G(p.Ala27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A27V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEAF1
ENST00000382409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.759

Variant links:

Genes affected

DEAF1 (HGNC:14677): (DEAF1 transcription factor) This gene encodes a zinc finger domain-containing protein that functions as a regulator of transcription. The encoded proteins binds to its own promoter as well as to that of several target genes. Activity of this protein is important in the regulation of embryonic development. Mutations in this gene have been found in individuals with autosomal dominant cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

DEAF1 links:

EPS8L2 (HGNC:21296): (EPS8 signaling adaptor L2) This gene encodes a member of the EPS8 gene family. The encoded protein, like other members of the family, is thought to link growth factor stimulation to actin organization, generating functional redundancy in the pathways that regulate actin cytoskeletal remodeling. [provided by RefSeq, Dec 2008]

EPS8L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20514435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEAF1	NM_021008.4 linkuse as main transcript	c.80C>G	p.Ala27Gly	missense_variant	1/12	ENST00000382409.4	NP_066288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEAF1	ENST00000382409.4 linkuse as main transcript	c.80C>G	p.Ala27Gly	missense_variant	1/12	1	NM_021008.4	ENSP00000371846	P1	O75398-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

145146

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000245

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000174

AC:

AN:

919926

Hom.:

Cov.:

AF XY:

0.0000227

AC XY:

AN XY:

440526

show subpopulations

Gnomad4 AFR exome

AF:

0.0000579

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.000165

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000124

Gnomad4 OTH exome

AF:

0.0000617

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

145276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70842

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.80C>G (p.A27G) alteration is located in exon 1 (coding exon 1) of the DEAF1 gene. This alteration results from a C to G substitution at nucleotide position 80, causing the alanine (A) at amino acid position 27 to be replaced by a glycine (G). 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

0.24

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.94

N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.58

REVEL

Benign

0.053

Sift

Benign

0.11

Sift4G

Uncertain

0.032

Polyphen

0.42

Vest4

0.17

MutPred

0.35

Loss of stability (P = 0.1239);

MVP

0.57

MPC

1.6

ClinPred

0.56

GERP RS

2.4

Varity_R

0.083

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over