Variant chr12-57517377-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004083.6(DDIT3):c.30C>T(p.Phe10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,611,882 control chromosomes in the GnomAD database, including 19,096 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2524 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16572 hom. )

Consequence

DDIT3
NM_004083.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Variant links:

Genes affected

DDIT3 (HGNC:2726): (DNA damage inducible transcript 3) This gene encodes a member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, such as C/EBP and LAP (liver activator protein), and preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis, is activated by endoplasmic reticulum stress, and promotes apoptosis. Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in myxoid liposarcomas or Ewing sarcoma. Multiple alternatively spliced transcript variants encoding two isoforms with different length have been identified. [provided by RefSeq, Aug 2010]

DDIT3 links:

MARS1 (HGNC:6898): (methionyl-tRNA synthetase 1) This gene encodes a member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. The encoded protein is a component of the multi-tRNA synthetase complex and catalyzes the ligation of methionine to tRNA molecules. [provided by RefSeq, Jan 2011]

MARS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDIT3	NM_004083.6 linkuse as main transcript	c.30C>T	p.Phe10=	synonymous_variant	3/4	ENST00000346473.8	NP_004074.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDIT3	ENST00000346473.8 linkuse as main transcript	c.30C>T	p.Phe10=	synonymous_variant	3/4	1	NM_004083.6	ENSP00000340671	P1	P35638-1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26827

AN:

152004

Hom.:

2510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.166

AC:

41329

AN:

248778

Hom.:

3753

AF XY:

0.165

AC XY:

22262

AN XY:

134718

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.286

Gnomad SAS exome

AF:

0.149

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.146

AC:

213695

AN:

1459758

Hom.:

16572

Cov.:

AF XY:

0.146

AC XY:

106281

AN XY:

726270

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.217

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.137

Gnomad4 OTH exome

AF:

0.161

GnomAD4 genome

AF:

0.177

AC:

26872

AN:

152124

Hom.:

2524

Cov.:

AF XY:

0.182

AC XY:

13532

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.263

Gnomad4 SAS

AF:

0.160

Gnomad4 FIN

AF:

0.226

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.148

Hom.:

2057

Bravo

AF:

0.175

Asia WGS

AF:

0.175

AC:

612

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.1

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -15

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over