Variant 13-50843474-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001306135.2(DLEU7):c.173G>A(p.Arg58Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,330,460 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 1 hom. )

Consequence

DLEU7
NM_001306135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.137

Variant links:

Genes affected

DLEU7 (HGNC:17567): (deleted in lymphocytic leukemia 7)

DLEU7 links:

DLEU1 (HGNC:13747): (deleted in lymphocytic leukemia 1)

DLEU1 links:

DLEU7-AS1 (HGNC:):

DLEU7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045990318).

BS2

High AC in GnomAd at 69 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DLEU7	NM_001306135.2 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	1/2	ENST00000504404.2
DLEU7-AS1	NR_046551.1 linkuse as main transcript	n.438+3380C>T		intron_variant, non_coding_transcript_variant
DLEU7	NM_198989.3 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLEU7	ENST00000504404.2 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	1/2	1	NM_001306135.2	P1	Q6UYE1-1

Frequencies

GnomAD3 genomes

AF:

0.000456

AC:

AN:

151346

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000399

Gnomad OTH

AF:

0.00240

GnomAD4 exome

AF:

0.000358

AC:

422

AN:

1179004

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

191

AN XY:

566518

show subpopulations

Gnomad4 AFR exome

AF:

0.000859

Gnomad4 AMR exome

AF:

0.000578

Gnomad4 ASJ exome

AF:

0.00351

Gnomad4 EAS exome

AF:

0.0000372

Gnomad4 SAS exome

AF:

0.000214

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.000989

GnomAD4 genome

AF:

0.000462

AC:

AN:

151456

Hom.:

Cov.:

AF XY:

0.000486

AC XY:

AN XY:

74076

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00112

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000399

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.000212

Hom.:

Bravo

AF:

0.000657

ExAC

AF:

0.000141

AC:

Asia WGS

AF:

0.000579

AC:

AN:

3470

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2022

The c.173G>A (p.R58Q) alteration is located in exon 1 (coding exon 1) of the DLEU7 gene. This alteration results from a G to A substitution at nucleotide position 173, causing the arginine (R) at amino acid position 58 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.029

Sift

Benign

0.12

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.062

B;B

Vest4

0.17

MVP

0.13

MPC

1.7

ClinPred

0.32

GERP RS

0.16

Varity_R

0.049

gMVP

0.13

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over