Variant 4-100187729-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_145244.4(DDIT4L):c.530T>C(p.Val177Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000683 in 1,609,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DDIT4L
NM_145244.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.82

Variant links:

Genes affected

DDIT4L (HGNC:30555): (DNA damage inducible transcript 4 like) Predicted to be involved in negative regulation of signal transduction. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DDIT4L links:

H2AZ1-DT (HGNC:):

H2AZ1-DT 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=0.35669005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDIT4L	NM_145244.4 linkuse as main transcript	c.530T>C	p.Val177Ala	missense_variant	3/3	ENST00000273990.6	NP_660287.1	Q96D03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDIT4L	ENST00000273990.6 linkuse as main transcript	c.530T>C	p.Val177Ala	missense_variant	3/3	1	NM_145244.4	ENSP00000354830.2	Q96D03
DDIT4L	ENST00000502763.1 linkuse as main transcript	c.530T>C	p.Val177Ala	missense_variant, splice_region_variant	2/2	2		ENSP00000427301.1	D6RJ99
H2AZ1-DT	ENST00000515026.1 linkuse as main transcript	n.730-7336A>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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

GnomAD3 exomes

AF:

0.00000810

AC:

AN:

246966

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133496

show subpopulations

Gnomad AFR exome

AF:

0.000125

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457580

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724972

show subpopulations

Gnomad4 AFR exome

AF:

0.0000606

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000217

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

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

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

Nov 09, 2021

The c.530T>C (p.V177A) alteration is located in exon 3 (coding exon 2) of the DDIT4L gene. This alteration results from a T to C substitution at nucleotide position 530, causing the valine (V) at amino acid position 177 to be replaced by an alanine (A). 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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.22

Sift

Benign

0.064

T;D

Sift4G

Benign

0.16

T;D

Polyphen

0.78

P;.

Vest4

0.37

MVP

0.75

MPC

0.16

ClinPred

0.69

GERP RS

6.0

Varity_R

0.12

gMVP

0.36

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