rs758222466

Variant names:

• chr6-73353864-C-A
• rs758222466
• NM_001025290.3:c.281G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-73353864-C-A
• chr6-73353864-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025290.3(DPPA5):​c.281G>T​(p.Arg94Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. R94H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPPA5 NM_001025290.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 1 publications found

Genes affected

DPPA5 (HGNC:19201): (developmental pluripotency associated 5) This gene encodes a protein that may function in the control of cell pluripotency and early embryogenesis. Expression of this gene is a specific marker for pluripotent stem cells. Pseudogenes of this gene are located on the short arm of chromosome 10 and the long arm of chromosomes 14 and 19. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24354532).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025290.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPPA5	NM_001025290.3	MANE Select	c.281G>T	p.Arg94Leu	missense	Exon 2 of 3	NP_001020461.1	A6NC42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPPA5	ENST00000370370.4	TSL:1 MANE Select	c.281G>T	p.Arg94Leu	missense	Exon 2 of 3	ENSP00000359396.3	A6NC42

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250130 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461088 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726836

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5406

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111868

Other (OTH) AF: 0.00 AC: 0 AN: 60306

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.33
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.073
Sift	Benign	0.30	T
Sift4G	Benign	0.34	T
Polyphen		0.010	B
Vest4		0.71
MutPred		0.34		Loss of disorder (P = 0.0294)
MVP		0.19
MPC		0.96
ClinPred		0.058	T
GERP RS		2.9
PromoterAI		-0.015	Neutral
Varity_R		0.071
gMVP		0.83
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs758222466; hg19: chr6-74063587;