rs747752742

Variant names:

• chr4-100187748-T-A
• rs747752742
• NM_145244.4:c.511A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-100187748-T-A
• chr4-100187748-T-C
• chr4-100187748-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145244.4(DDIT4L):​c.511A>T​(p.Ser171Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. S171G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DDIT4L NM_145244.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDIT4L	NM_145244.4	c.511A>T	p.Ser171Cys	missense_variant	Exon 3 of 3	ENST00000273990.6	NP_660287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDIT4L	ENST00000273990.6	c.511A>T	p.Ser171Cys	missense_variant	Exon 3 of 3	1	NM_145244.4	ENSP00000354830.2
DDIT4L	ENST00000502763.1	c.511A>T	p.Ser171Cys	missense_variant	Exon 2 of 2	2		ENSP00000427301.1
H2AZ1-DT	ENST00000515026.1	n.730-7317T>A		intron_variant	Intron 5 of 5	5
DDIT4L	ENST00000513992.1	c.*127A>T		downstream_gene_variant		4		ENSP00000427040.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		1.0	D;.
Vest4		0.49
MutPred		0.81		Loss of disorder (P = 0.0475);Loss of disorder (P = 0.0475);
MVP		0.85
MPC		0.22
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.44
gMVP		0.62

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: rs747752742; hg19: chr4-101108905;