5-10683530-C-A

Variant names:

• chr5-10683530-C-A
• NM_004394.3:c.194G>T

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: Splicing: ADA: 0.07889
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72

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]

ACMG classification

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
DAP	NM_004394.3	c.194G>T	p.Arg65Leu	missense_variant, splice_region_variant	Exon 3 of 4	ENST00000230895.11	NP_004385.1
DAP	NM_001291963.2	c.153-2361G>T		intron_variant	Intron 2 of 2		NP_001278892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAP	ENST00000230895.11	c.194G>T	p.Arg65Leu	missense_variant, splice_region_variant	Exon 3 of 4	1	NM_004394.3	ENSP00000230895.7
DAP	ENST00000432074.2	c.153-2361G>T		intron_variant	Intron 2 of 2	2		ENSP00000394163.2
DAP	ENST00000508253.5	n.351G>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
DAP	ENST00000514882.5	n.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

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;