dbSNP rs148736800: DDIT4:p.Ser194Thr (chr10-72275070-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_019058.4(DDIT4):c.581G>C(p.Ser194Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,613,532 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 2 hom. )

Consequence

DDIT4
NM_019058.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.02

Variant links:

Genes affected

DDIT4 (HGNC:24944): (DNA damage inducible transcript 4) Predicted to enable 14-3-3 protein binding activity. Involved in defense response to virus; negative regulation of TOR signaling; and response to hypoxia. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

DDIT4 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=0.0100539625).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDIT4	NM_019058.4 link	c.581G>C	p.Ser194Thr	missense_variant	Exon 3 of 3	ENST00000307365.4	NP_061931.1	Q9NX09A0A024QZQ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDIT4	ENST00000307365.4 link	c.581G>C	p.Ser194Thr	missense_variant	Exon 3 of 3	1	NM_019058.4	ENSP00000307305.3		Q9NX09

Frequencies

GnomAD3 genomes

AF:

0.000729

AC:

111

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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

GnomAD3 exomes

AF:

0.000220

AC:

AN:

250098

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135476

show subpopulations

Gnomad AFR exome

AF:

0.00292

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000862

AC:

126

AN:

1461198

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.00290

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152334

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.000392

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

Bravo

AF:

0.000888

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000280

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.25

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.62

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.070

REVEL

Benign

0.042

Sift

Benign

0.30

Sift4G

Benign

0.65

Polyphen

0.097

Vest4

0.11

MVP

0.60

MPC

0.39

ClinPred

0.016

GERP RS

5.0

Varity_R

0.40

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over