10-72274226-C-G

Variant names:

• chr10-72274226-C-G
• rs756710581
• NM_019058.4:c.10C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019058.4(DDIT4):​c.10C>G​(p.Leu4Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3094387).

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.10C>G	p.Leu4Val	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.10C>G	p.Leu4Val	missense	Exon 2 of 3	ENSP00000307305.3	Q9NX09
	DDIT4	ENST00000473155.2	TSL:1	n.303C>G		non_coding_transcript_exon	Exon 1 of 2
	DDIT4	ENST00000871236.1		c.10C>G	p.Leu4Val	missense	Exon 2 of 3	ENSP00000541295.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.079
Sift	Benign	0.085	T
Sift4G	Benign	0.41	T
Polyphen		0.99	D
Vest4		0.33
MutPred		0.19		Loss of helix (P = 0.079)
MVP		0.74
MPC		0.93
ClinPred		0.85	D
GERP RS		4.6
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.15
Mutation Taster		=95/5	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

dbSNP: rs756710581; hg19: chr10-74033984;