chr3-16264824-T-C

Variant names:

• chr3-16264824-T-C
• rs767196710
• NM_206831.3:c.53A>G

Variant summary

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

The NM_206831.3(DPH3):​c.53A>G​(p.Asp18Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPH3 NM_206831.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.46
• Publications: 0 publications found

Genes affected

DPH3 (HGNC:27717): (diphthamide biosynthesis 3) This gene encodes a CSL zinc finger-containing protein that is required for dipthamide biosynthesis. The encoded protein is necessary for the initial step in the modification of a histidine residue in elongation factor-2 to diphthamide. This modified residue is a target for ADP ribosylation by the bacterial toxins diphtheria toxin and Pseudomonas exotoxin A. Alternative splicing results in multiple transcript variants that encode the same isoform. [provided by RefSeq, Feb 2009]

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=0.2794969).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206831.3. 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
	DPH3	NM_206831.3	MANE Select	c.53A>G	p.Asp18Gly	missense	Exon 1 of 3	NP_996662.1	Q96FX2-1
	DPH3	NM_001047434.3		c.53A>G	p.Asp18Gly	missense	Exon 1 of 2	NP_001040899.1	Q96FX2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPH3	ENST00000488423.2	TSL:1 MANE Select	c.53A>G	p.Asp18Gly	missense	Exon 1 of 3	ENSP00000419599.1	Q96FX2-1
	DPH3	ENST00000953358.1		c.53A>G	p.Asp18Gly	missense	Exon 1 of 3	ENSP00000623417.1
	DPH3	ENST00000383775.4	TSL:2	c.53A>G	p.Asp18Gly	missense	Exon 1 of 2	ENSP00000373285.4	Q96FX2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.60	T
PhyloP100		6.5
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.18
Sift	Benign	0.093	T
Sift4G	Uncertain	0.053	T
Polyphen		0.30	B
Vest4		0.39
MutPred		0.42		Gain of catalytic residue at D18 (P = 0.0808)
MVP		0.56
MPC		0.18
ClinPred		1.0	D
GERP RS		5.2
PromoterAI		-0.011	Neutral
Varity_R		0.61
gMVP		0.42
Mutation Taster		=55/45	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: rs767196710; hg19: chr3-16306331;