NM_004394.3:c.*621A>G

Variant names:

• chr5-10680435-T-C
• rs9857
• NM_004394.3:c.*621A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004394.3(DAP):​c.*621A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 418,666 control chromosomes in the GnomAD database, including 18,649 homozygotes. 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: 𝑓 0.31 (7783 hom., cov: 33)
  • Exomes 𝑓: 0.28 (10866 hom.)
• Consequence: DAP NM_004394.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004394.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAP	NM_004394.3	MANE Select	c.*621A>G		3_prime_UTR	Exon 4 of 4	NP_004385.1
	DAP	NM_001291963.2		c.*272A>G		3_prime_UTR	Exon 3 of 3	NP_001278892.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAP	ENST00000230895.11	TSL:1 MANE Select	c.*621A>G		3_prime_UTR	Exon 4 of 4	ENSP00000230895.7
	DAP	ENST00000432074.2	TSL:2	c.*272A>G		splice_region	Exon 3 of 3	ENSP00000394163.2
	DAP	ENST00000432074.2	TSL:2	c.*272A>G		3_prime_UTR	Exon 3 of 3	ENSP00000394163.2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46969 AN: 152004 Hom.: 7765 Cov.: 33

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.276 AC: 73444 AN: 266544 Hom.: 10866 Cov.: 0 AF XY: 0.279 AC XY: 38721 AN XY: 139024

African (AFR) AF: 0.397 AC: 3153 AN: 7942

American (AMR) AF: 0.273 AC: 2401 AN: 8798

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 2226 AN: 8932

East Asian (EAS) AF: 0.419 AC: 7106 AN: 16946

South Asian (SAS) AF: 0.335 AC: 8686 AN: 25966

European-Finnish (FIN) AF: 0.187 AC: 2680 AN: 14300

Middle Eastern (MID) AF: 0.385 AC: 467 AN: 1212

European-Non Finnish (NFE) AF: 0.254 AC: 42287 AN: 166410

Other (OTH) AF: 0.277 AC: 4438 AN: 16038

GnomAD4 genome AF: 0.309 AC: 47019 AN: 152122 Hom.: 7783 Cov.: 33 AF XY: 0.308 AC XY: 22902 AN XY: 74370

African (AFR) AF: 0.412 AC: 17104 AN: 41488

American (AMR) AF: 0.284 AC: 4338 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3472

East Asian (EAS) AF: 0.447 AC: 2310 AN: 5168

South Asian (SAS) AF: 0.373 AC: 1801 AN: 4822

European-Finnish (FIN) AF: 0.195 AC: 2069 AN: 10596

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17383 AN: 67972

Other (OTH) AF: 0.318 AC: 670 AN: 2110

Alfa AF: 0.275 Hom.: 10217

Bravo AF: 0.318

Asia WGS AF: 0.434 AC: 1509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.48
PhyloP100		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs9857; hg19: chr5-10680547;