5-10683530-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004394.3(DAP):​c.194G>T​(p.Arg65Leu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R65W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DAP
NM_004394.3 missense, splice_region

Scores

2
10
7
Splicing: ADA: 0.07889
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72
Variant links:
Genes affected
DAP (HGNC:2672): (death associated protein) This gene encodes a basic, proline-rich, 15-kD protein. The protein acts as a positive mediator of programmed cell death that is induced by interferon-gamma. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DAPNM_004394.3 linkc.194G>T p.Arg65Leu missense_variant, splice_region_variant Exon 3 of 4 ENST00000230895.11 NP_004385.1 P51397
DAPNM_001291963.2 linkc.153-2361G>T intron_variant Intron 2 of 2 NP_001278892.1 P51397B4DQ75

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DAPENST00000230895.11 linkc.194G>T p.Arg65Leu missense_variant, splice_region_variant Exon 3 of 4 1 NM_004394.3 ENSP00000230895.7 P51397
DAPENST00000432074.2 linkc.153-2361G>T intron_variant Intron 2 of 2 2 ENSP00000394163.2 B4DQ75
DAPENST00000508253.5 linkn.351G>T non_coding_transcript_exon_variant Exon 3 of 3 2
DAPENST00000514882.5 linkn.262G>T non_coding_transcript_exon_variant Exon 3 of 4 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.194G>T (p.R65L) alteration is located in exon 3 (coding exon 3) of the DAP gene. This alteration results from a G to T substitution at nucleotide position 194, causing the arginine (R) at amino acid position 65 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
Pathogenic
0.88
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.087
T
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.59
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Benign
0.13
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.012
D
Polyphen
0.76
P
Vest4
0.74
MutPred
0.36
Loss of ubiquitination at K68 (P = 0.0398);
MVP
0.65
MPC
0.35
ClinPred
0.97
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.079
dbscSNV1_RF
Benign
0.23
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-10683642; API