rs532671271

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021008.4(DEAF1):​c.1663G>C​(p.Val555Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. V555M) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

DEAF1
NM_021008.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.94
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1709899).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DEAF1NM_021008.4 linkc.1663G>C p.Val555Leu missense_variant Exon 12 of 12 ENST00000382409.4 NP_066288.2 O75398-1
DEAF1NM_001293634.1 linkc.1438G>C p.Val480Leu missense_variant Exon 11 of 11 NP_001280563.1 O75398-5
DEAF1NM_001367390.1 linkc.937G>C p.Val313Leu missense_variant Exon 12 of 12 NP_001354319.1
DEAF1XM_047426251.1 linkc.937G>C p.Val313Leu missense_variant Exon 12 of 12 XP_047282207.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DEAF1ENST00000382409.4 linkc.1663G>C p.Val555Leu missense_variant Exon 12 of 12 1 NM_021008.4 ENSP00000371846.3 O75398-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460890
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726782
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.24
T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.6
L
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.94
N
REVEL
Benign
0.085
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.039
D
Polyphen
0.67
P
Vest4
0.18
MutPred
0.25
Gain of helix (P = 0.062);
MVP
0.67
MPC
1.6
ClinPred
0.66
D
GERP RS
3.3
Varity_R
0.080
gMVP
0.13

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.

Other links and lift over

dbSNP: rs532671271; hg19: chr11-644585; API