Variant 4-100188050-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145244.4(DDIT4L):c.209A>T(p.Gln70Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,836 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: not found (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: 1.65

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDIT4L	NM_145244.4 linkuse as main transcript	c.209A>T	p.Gln70Leu	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.209A>T	p.Gln70Leu	missense_variant	3/3	1	NM_145244.4	ENSP00000354830.2	Q96D03
DDIT4L	ENST00000502763.1 linkuse as main transcript	c.209A>T	p.Gln70Leu	missense_variant	2/2	2		ENSP00000427301.1	D6RJ99
DDIT4L	ENST00000513992.1 linkuse as main transcript	c.209A>T	p.Gln70Leu	missense_variant	3/3	4		ENSP00000427040.1	D6RD49
H2AZ1-DT	ENST00000515026.1 linkuse as main transcript	n.730-7015T>A		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251378

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

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:

1461836

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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

Cov.:

Bravo

AF:

0.00000756

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

Oct 05, 2021

The c.209A>T (p.Q70L) alteration is located in exon 3 (coding exon 2) of the DDIT4L gene. This alteration results from a A to T substitution at nucleotide position 209, causing the glutamine (Q) at amino acid position 70 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.037

T;.;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

L;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.061

Sift

Benign

0.46

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0090

B;.;.

Vest4

0.27

MutPred

0.39

Loss of disorder (P = 0.0723);Loss of disorder (P = 0.0723);Loss of disorder (P = 0.0723);

MVP

0.56

MPC

0.034

ClinPred

0.14

GERP RS

4.5

Varity_R

0.12

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.30

Position offset: -23

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