chr5-10680885-G-A

Position:

• chr5-10680885-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291963.2(DAP):​c.437C>T​(p.Ser146Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,536,988 control chromosomes in the GnomAD database, including 4,757 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.056 (321 hom., cov: 33)
  • Exomes 𝑓: 0.077 (4436 hom.)
• Consequence: DAP NM_001291963.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.600

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024189353).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAP	NM_004394.3	c.*171C>T		3_prime_UTR_variant	4/4	ENST00000230895.11	NP_004385.1
DAP	NM_001291963.2	c.437C>T	p.Ser146Phe	missense_variant	3/3		NP_001278892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAP	ENST00000230895	c.*171C>T		3_prime_UTR_variant	4/4	1	NM_004394.3	ENSP00000230895.7
DAP	ENST00000432074.2	c.437C>T	p.Ser146Phe	missense_variant	3/3	2		ENSP00000394163.2

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8540 AN: 152178 Hom.: 321 Cov.: 33

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0850

Gnomad OTH AF: 0.0617

GnomAD3 exomes AF: 0.0553 AC: 8016 AN: 144910 Hom.: 320 AF XY: 0.0549 AC XY: 4244 AN XY: 77320

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.0443

Gnomad ASJ exome AF: 0.0554

Gnomad EAS exome AF: 0.00178

Gnomad SAS exome AF: 0.0183

Gnomad FIN exome AF: 0.0753

Gnomad NFE exome AF: 0.0859

Gnomad OTH exome AF: 0.0700

GnomAD4 exome AF: 0.0769 AC: 106416 AN: 1384692 Hom.: 4436 Cov.: 32 AF XY: 0.0754 AC XY: 51541 AN XY: 683264

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.0458

Gnomad4 ASJ exome AF: 0.0570

Gnomad4 EAS exome AF: 0.000558

Gnomad4 SAS exome AF: 0.0197

Gnomad4 FIN exome AF: 0.0803

Gnomad4 NFE exome AF: 0.0875

Gnomad4 OTH exome AF: 0.0680

GnomAD4 genome AF: 0.0561 AC: 8537 AN: 152296 Hom.: 321 Cov.: 33 AF XY: 0.0537 AC XY: 3999 AN XY: 74464

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.0503

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.0744

Gnomad4 NFE AF: 0.0850

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0730 Hom.: 310

Bravo AF: 0.0526

TwinsUK AF: 0.0850 AC: 315

ALSPAC AF: 0.0864 AC: 333

ExAC AF: 0.0346 AC: 1104

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	5.0
DANN	Uncertain	1.0
Eigen	Benign	-0.031
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.76	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.077
ClinPred		0.015	T
GERP RS		3.7
gMVP		0.011

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

Other links and lift over

dbSNP: rs5745297; hg19: chr5-10680997; COSMIC: COSV50143482; COSMIC: COSV50143482;