Variant chr4-100189911-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_145244.4(DDIT4L):c.73C>T(p.Pro25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,614,036 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 4 hom. )

Consequence

DDIT4L
NM_145244.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

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:40271): (H2AZ1 divergent transcript)

H2AZ1-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008774757).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDIT4L	NM_145244.4 linkuse as main transcript	c.73C>T	p.Pro25Ser	missense_variant	2/3	ENST00000273990.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DDIT4L	ENST00000273990.6 linkuse as main transcript	c.73C>T	p.Pro25Ser	missense_variant	2/3	1	NM_145244.4	P1
H2AZ1-DT	ENST00000515026.1 linkuse as main transcript	n.730-5154G>A		intron_variant, non_coding_transcript_variant		5
DDIT4L	ENST00000502763.1 linkuse as main transcript	c.73C>T	p.Pro25Ser	missense_variant	1/2	2
DDIT4L	ENST00000513992.1 linkuse as main transcript	c.73C>T	p.Pro25Ser	missense_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000298

AC:

AN:

251354

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000195

AC:

285

AN:

1461778

Hom.:

Cov.:

AF XY:

0.000234

AC XY:

170

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00321

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000164

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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

Sep 15, 2021

The c.73C>T (p.P25S) alteration is located in exon 2 (coding exon 1) of the DDIT4L gene. This alteration results from a C to T substitution at nucleotide position 73, causing the proline (P) at amino acid position 25 to be replaced by a serine (S). 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

0.074

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0077

T;.;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.49

T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0088

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

0.25

N;N;N

REVEL

Benign

0.064

Sift

Benign

0.077

T;T;T

Sift4G

Benign

0.74

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.14

MVP

0.33

MPC

0.029

ClinPred

0.017

GERP RS

3.4

Varity_R

0.028

gMVP

0.25

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