Genetic Variant NM_021008.4:c.56T>G (chr11-694992-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021008.4(DEAF1):c.56T>G(p.Val19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 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. V19A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEAF1
NM_021008.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.125

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive 106
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EPS8L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.151497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEAF1	NM_021008.4 link	c.56T>G	p.Val19Gly	missense_variant	Exon 1 of 12	ENST00000382409.4	NP_066288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEAF1	ENST00000382409.4 link	c.56T>G	p.Val19Gly	missense_variant	Exon 1 of 12	1	NM_021008.4	ENSP00000371846.3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

144464

Hom.:

Cov.:

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:

0.00

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: AC0

AF:

0.00

AC:

AN:

916440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

439328

African (AFR)

AF:

0.00

AC:

AN:

17128

American (AMR)

AF:

0.00

AC:

AN:

5062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9854

East Asian (EAS)

AF:

0.00

AC:

AN:

11248

South Asian (SAS)

AF:

0.00

AC:

AN:

25598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2090

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

806354

Other (OTH)

AF:

0.00

AC:

AN:

32052

GnomAD4 genome

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

AF:

0.00

AC:

AN:

144464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70360

African (AFR)

AF:

0.00

AC:

AN:

39864

American (AMR)

AF:

0.00

AC:

AN:

14506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

4224

South Asian (SAS)

AF:

0.00

AC:

AN:

3888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65994

Other (OTH)

AF:

0.00

AC:

AN:

2030

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.34

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

PhyloP100

0.13

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.050

REVEL

Benign

0.080

Sift

Uncertain

0.015

Sift4G

Uncertain

0.021

Polyphen

0.022

Vest4

0.14

MutPred

0.35

Loss of stability (P = 0.1052);

MVP

0.39

MPC

0.81

ClinPred

0.097

GERP RS

1.3

PromoterAI

-0.14

Neutral

(source)

Varity_R

0.15

gMVP

0.25

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over