Variant 13-50843460-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001306135.2(DLEU7):c.187C>A(p.Pro63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000302 in 1,325,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

DLEU7
NM_001306135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.771

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:39966): (DLEU7 antisense RNA 1)

DLEU7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06554708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLEU7	NM_001306135.2 link	c.187C>A	p.Pro63Thr	missense_variant	1/2	ENST00000504404.2	NP_001293064.1	Q6UYE1-1
DLEU7	NM_198989.3 link	c.187C>A	p.Pro63Thr	missense_variant	1/2		NP_945340.2	Q6UYE1-2
DLEU7-AS1	NR_046551.1 link	n.438+3366G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLEU7	ENST00000504404.2 link	c.187C>A	p.Pro63Thr	missense_variant	1/2	1	NM_001306135.2	ENSP00000427177.1		Q6UYE1-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000170

AC:

AN:

1173684

Hom.:

Cov.:

AF XY:

0.00000177

AC XY:

AN XY:

563484

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151408

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.0000416

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

Mar 04, 2024

The c.187C>A (p.P63T) 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 187, causing the proline (P) at amino acid position 63 to be replaced by a threonine (T). 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

0.079

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.0

DANN

Benign

0.79

DEOGEN2

Benign

0.0050

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.066

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.4

D;N

REVEL

Benign

0.025

Sift

Benign

0.26

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.049

B;B

Vest4

0.092

MutPred

0.29

Gain of phosphorylation at P63 (P = 4e-04);Gain of phosphorylation at P63 (P = 4e-04);

MVP

0.17

MPC

0.98

ClinPred

0.16

GERP RS

-1.9

Varity_R

0.049

gMVP

0.095

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