Variant 13-50843338-G-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.309C>A(p.Phe103Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,476,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

DLEU7
NM_001306135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

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

DLEU7 links:

DLEU1 (HGNC:):

DLEU1 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=0.009743273).

BS2

High AC in GnomAdExome4 at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLEU7	NM_001306135.2 linkuse as main transcript	c.309C>A	p.Phe103Leu	missense_variant	1/2	ENST00000504404.2	NP_001293064.1	Q6UYE1-1
DLEU7	NM_198989.3 linkuse as main transcript	c.309C>A	p.Phe103Leu	missense_variant	1/2		NP_945340.2	Q6UYE1-2
DLEU7-AS1	NR_046551.1 linkuse as main transcript	n.438+3244G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLEU7	ENST00000504404.2 linkuse as main transcript	c.309C>A	p.Phe103Leu	missense_variant	1/2	1	NM_001306135.2	ENSP00000427177.1		Q6UYE1-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000893

AC:

AN:

100832

Hom.:

AF XY:

0.000106

AC XY:

AN XY:

56576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000688

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000651

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1323806

Hom.:

Cov.:

AF XY:

0.0000370

AC XY:

AN XY:

648796

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000382

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000462

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.55e-7

Gnomad4 OTH exome

AF:

0.0000369

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000608

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 20, 2023

The c.309C>A (p.F103L) alteration is located in exon 1 (coding exon 1) of the DLEU7 gene. This alteration results from a C to A substitution at nucleotide position 309, causing the phenylalanine (F) at amino acid position 103 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.026

DANN

Benign

0.77

DEOGEN2

Benign

0.011

.;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0082

MetaRNN

Benign

0.0097

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

L;L

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.7

D;N

REVEL

Benign

0.015

Sift

Benign

0.62

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.19

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.040

MPC

0.97

ClinPred

0.024

GERP RS

-8.2

Varity_R

0.038

gMVP

0.054

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