5-10681071-C-T

Variant names:

• chr5-10681071-C-T
• rs957397251
• NM_004394.3:c.294G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004394.3(DAP):​c.294G>A​(p.Gln98Gln) variant causes a synonymous 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DAP NM_004394.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09693259).
• BP7: Synonymous conserved (PhyloP=1.42 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAP	NM_004394.3	c.294G>A	p.Gln98Gln	synonymous_variant	Exon 4 of 4	ENST00000230895.11	NP_004385.1
DAP	NM_001291963.2	c.251G>A	p.Ser84Asn	missense_variant	Exon 3 of 3		NP_001278892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAP	ENST00000230895.11	c.294G>A	p.Gln98Gln	synonymous_variant	Exon 4 of 4	1	NM_004394.3	ENSP00000230895.7
DAP	ENST00000432074.2	c.251G>A	p.Ser84Asn	missense_variant	Exon 3 of 3	2		ENSP00000394163.2
DAP	ENST00000514882.5	n.*20G>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1445544 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 716780

African (AFR) AF: 0.00 AC: 0 AN: 33314

American (AMR) AF: 0.00 AC: 0 AN: 42778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25720

East Asian (EAS) AF: 0.00 AC: 0 AN: 39248

South Asian (SAS) AF: 0.00 AC: 0 AN: 83588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103260

Other (OTH) AF: 0.00 AC: 0 AN: 59648

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	7.3
DANN	Uncertain	0.99
Eigen	Benign	0.083
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.16	T
Polyphen		0.70	P
Vest4		0.11
MVP		0.41
ClinPred		0.85	D
GERP RS		3.1
gMVP		0.0059
Mutation Taster		=94/6	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: rs957397251; hg19: chr5-10681183;