4-100187867-A-G

Position:

• chr4-100187867-A-G

Variant summary

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

The NM_145244.4(DDIT4L):​c.392T>C​(p.Val131Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: DDIT4L NM_145244.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

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]

H2AZ1-DT (HGNC:):

ACMG classification

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	c.392T>C	p.Val131Ala	missense_variant	3/3	ENST00000273990.6	NP_660287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDIT4L	ENST00000273990.6	c.392T>C	p.Val131Ala	missense_variant	3/3	1	NM_145244.4	ENSP00000354830.2
DDIT4L	ENST00000502763.1	c.392T>C	p.Val131Ala	missense_variant	2/2	2		ENSP00000427301.1
H2AZ1-DT	ENST00000515026.1	n.730-7198A>G		intron_variant		5
DDIT4L	ENST00000513992.1	c.*8T>C		downstream_gene_variant		4		ENSP00000427040.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461432 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 726988

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.392T>C (p.V131A) alteration is located in exon 3 (coding exon 2) of the DDIT4L gene. This alteration results from a T to C substitution at nucleotide position 392, causing the valine (V) at amino acid position 131 to be replaced by an alanine (A). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.022
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.19
Sift	Benign	0.087	T;D
Sift4G	Uncertain	0.045	D;D
Polyphen		0.043	B;.
Vest4		0.16
MutPred		0.90		Loss of stability (P = 0.085);Loss of stability (P = 0.085);
MVP		0.63
MPC		0.034
ClinPred		0.83	D
GERP RS		4.5
Varity_R		0.11
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs997463567; hg19: chr4-101109024;