chr5-10761059-G-C

Variant names:

• chr5-10761059-G-C
• rs985733833
• NM_004394.3:c.10C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004394.3(DAP):​c.10C>G​(p.Pro4Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DAP NM_004394.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 0 publications found

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]

DAP-DT (HGNC:55214): (DAP divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26733696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAP	NM_004394.3	c.10C>G	p.Pro4Ala	missense_variant	Exon 1 of 4	ENST00000230895.11	NP_004385.1
DAP	NM_001291963.2	c.10C>G	p.Pro4Ala	missense_variant	Exon 1 of 3		NP_001278892.1
DAP-DT	NR_187555.1	n.24G>C		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAP	ENST00000230895.11	c.10C>G	p.Pro4Ala	missense_variant	Exon 1 of 4	1	NM_004394.3	ENSP00000230895.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.
PhyloP100		2.4
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.0	N;D
REVEL	Benign	0.15
Sift	Benign	0.15	T;T
Sift4G	Benign	0.26	T;T
Polyphen		1.0	D;D
Vest4		0.30
MutPred		0.13		Loss of catalytic residue at P4 (P = 0.0135);Loss of catalytic residue at P4 (P = 0.0135);
MVP		0.70
MPC		0.72
ClinPred		0.60	D
GERP RS		2.9
PromoterAI		0.015	Neutral
Varity_R		0.056
gMVP		0.0065
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs985733833; hg19: chr5-10761171;