chr4-100187794-A-C

Position:

• chr4-100187794-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145244.4(DDIT4L):​c.465T>G​(p.Phe155Leu) 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. 14/21 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: DDIT4L NM_145244.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.334

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:40271): (H2AZ1 divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0813494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDIT4L	NM_145244.4	c.465T>G	p.Phe155Leu	missense_variant	3/3	ENST00000273990.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDIT4L	ENST00000273990.6	c.465T>G	p.Phe155Leu	missense_variant	3/3	1	NM_145244.4	P1
H2AZ1-DT	ENST00000515026.1	n.730-7271A>C		intron_variant, non_coding_transcript_variant		5
DDIT4L	ENST00000502763.1	c.465T>G	p.Phe155Leu	missense_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Feb 05, 2024

The c.465T>G (p.F155L) alteration is located in exon 3 (coding exon 2) of the DDIT4L gene. This alteration results from a T to G substitution at nucleotide position 465, causing the phenylalanine (F) at amino acid position 155 to be replaced by a leucine (L). 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	Benign	0.32
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.4
DANN	Benign	0.88
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	0.82	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.77	N;N
REVEL	Benign	0.040
Sift	Benign	0.75	T;T
Sift4G	Benign	0.66	T;T
Polyphen		0.0	B;.
Vest4		0.13
MutPred		0.25		Loss of methylation at R157 (P = 0.1084);Loss of methylation at R157 (P = 0.1084);
MVP		0.17
MPC		0.031
ClinPred		0.037	T
GERP RS		-0.53
Varity_R		0.043
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-101108951;