rs201322046

Variant names:

• chr4-100189911-G-A
• rs201322046
• NM_145244.4:c.73C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-100189911-G-A
• chr4-100189911-G-C
• chr4-100189911-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_145244.4(DDIT4L):​c.73C>T​(p.Pro25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,614,036 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (4 hom.)
• Consequence: DDIT4L NM_145244.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58
• Publications: 3 publications found

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)

DDIT4L-AS1 (HGNC:55562): (DDIT4L antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008774757).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145244.4. 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
	DDIT4L	NM_145244.4	MANE Select	c.73C>T	p.Pro25Ser	missense	Exon 2 of 3	NP_660287.1	Q96D03
	DDIT4L-AS1	NR_125924.1		n.-122G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDIT4L	ENST00000273990.6	TSL:1 MANE Select	c.73C>T	p.Pro25Ser	missense	Exon 2 of 3	ENSP00000354830.2	Q96D03
	DDIT4L	ENST00000966423.1		c.73C>T	p.Pro25Ser	missense	Exon 2 of 3	ENSP00000636482.1
	DDIT4L	ENST00000502763.1	TSL:2	c.73C>T	p.Pro25Ser	missense	Exon 1 of 2	ENSP00000427301.1	D6RJ99

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152140 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000298 AC: 75 AN: 251354 AF XY: 0.000324

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00327

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000195 AC: 285 AN: 1461778 Hom.: 4 Cov.: 30 AF XY: 0.000234 AC XY: 170 AN XY: 727196

African (AFR) AF: 0.00173 AC: 58 AN: 33480

American (AMR) AF: 0.000604 AC: 27 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00321 AC: 84 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1111958

Other (OTH) AF: 0.000679 AC: 41 AN: 60394

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152258 Hom.: 2 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74440

African (AFR) AF: 0.000144 AC: 6 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000364 Hom.: 1

Bravo AF: 0.000257

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000222 AC: 27

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.6
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.064
Sift	Benign	0.077	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.14
MVP		0.33
MPC		0.029
ClinPred		0.017	T
GERP RS		3.4
PromoterAI		-0.034	Neutral
Varity_R		0.028
gMVP		0.25
Mutation Taster		=93/7	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: rs201322046; hg19: chr4-101111068;