NM_019058.4:c.11T>C

Variant names:

• chr10-72274227-T-C
• NM_019058.4:c.11T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019058.4(DDIT4):​c.11T>C​(p.Leu4Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L4F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DDIT4 NM_019058.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09
• Publications: 0 publications found

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-AS1 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019058.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDIT4	NM_019058.4	MANE Select	c.11T>C	p.Leu4Pro	missense	Exon 2 of 3	NP_061931.1	Q9NX09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDIT4	ENST00000307365.4	TSL:1 MANE Select	c.11T>C	p.Leu4Pro	missense	Exon 2 of 3	ENSP00000307305.3	Q9NX09
	DDIT4	ENST00000473155.2	TSL:1	n.304T>C		non_coding_transcript_exon	Exon 1 of 2
	DDIT4	ENST00000871236.1		c.11T>C	p.Leu4Pro	missense	Exon 2 of 3	ENSP00000541295.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.14
Sift	Benign	0.053	T
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.74
MutPred		0.23		Loss of MoRF binding (P = 0.0155)
MVP		0.70
MPC		1.5
ClinPred		0.84	D
GERP RS		5.5
PromoterAI		0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.47
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

hg19: chr10-74033985;