NM_019058.4:c.477C>G

Variant names:

• chr10-72274966-C-G
• NM_019058.4:c.477C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019058.4(DDIT4):​c.477C>G​(p.Ser159Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 0.151
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2272082).

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.477C>G	p.Ser159Arg	missense	Exon 3 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.477C>G	p.Ser159Arg	missense	Exon 3 of 3	ENSP00000307305.3	Q9NX09
	DDIT4	ENST00000473155.2	TSL:1	n.770C>G		non_coding_transcript_exon	Exon 2 of 2
	DDIT4	ENST00000871236.1		c.477C>G	p.Ser159Arg	missense	Exon 3 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.032
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.15
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.16
Sift	Benign	0.21	T
Sift4G	Benign	0.32	T
Polyphen		0.85	P
Vest4		0.19
MutPred		0.37		Gain of sheet (P = 0.039)
MVP		0.59
MPC		1.3
ClinPred		0.94	D
GERP RS		2.3
Varity_R		0.29
gMVP		0.50
Mutation Taster		=59/41	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: chr10-74034724;