8-13499310-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182643.3(DLC1):​c.762A>T​(p.Gln254His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DLC1
NM_182643.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.422
Variant links:
Genes affected
DLC1 (HGNC:2897): (DLC1 Rho GTPase activating protein) This gene encodes a GTPase-activating protein (GAP) that is a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins. GAP family proteins participate in signaling pathways that regulate cell processes involved in cytoskeletal changes. This gene functions as a tumor suppressor gene in a number of common cancers, including prostate, lung, colorectal, and breast cancers. Multiple transcript variants due to alternative promoters and alternative splicing have been found for this gene.[provided by RefSeq, Apr 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.069595486).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DLC1NM_182643.3 linkuse as main transcriptc.762A>T p.Gln254His missense_variant 2/18 ENST00000276297.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DLC1ENST00000276297.9 linkuse as main transcriptc.762A>T p.Gln254His missense_variant 2/181 NM_182643.3 Q96QB1-2
DLC1ENST00000511869.1 linkuse as main transcriptc.762A>T p.Gln254His missense_variant 2/51 Q96QB1-5
DLC1ENST00000316609.9 linkuse as main transcriptc.762A>T p.Gln254His missense_variant 2/62 Q96QB1-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1461782
Hom.:
0
Cov.:
77
AF XY:
0.00
AC XY:
0
AN XY:
727188
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.077
DANN
Benign
0.81
DEOGEN2
Benign
0.068
T;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.50
T;.;.
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.070
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.1
L;L;L
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.44
N;N;N
REVEL
Benign
0.023
Sift
Benign
0.21
T;T;T
Sift4G
Benign
0.13
T;T;T
Polyphen
0.0
B;B;.
Vest4
0.080
MutPred
0.14
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
0.20
MPC
0.023
ClinPred
0.067
T
GERP RS
-5.6
Varity_R
0.065
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.

Other links and lift over

dbSNP: rs11203495; hg19: chr8-13356819; API