rs767196710

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-16264824-T-A
• chr3-16264824-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_206831.3(DPH3):​c.53A>T​(p.Asp18Val) variant causes a missense change. The variant allele was found at a frequency of 0.000052 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D18G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: DPH3 NM_206831.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031496882).

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>T	p.Asp18Val	missense	Exon 1 of 3	NP_996662.1	Q96FX2-1
	DPH3	NM_001047434.3		c.53A>T	p.Asp18Val	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>T	p.Asp18Val	missense	Exon 1 of 3	ENSP00000419599.1	Q96FX2-1
	DPH3	ENST00000953358.1		c.53A>T	p.Asp18Val	missense	Exon 1 of 3	ENSP00000623417.1
	DPH3	ENST00000383775.4	TSL:2	c.53A>T	p.Asp18Val	missense	Exon 1 of 2	ENSP00000373285.4	Q96FX2-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000278 AC: 70 AN: 251416 AF XY: 0.000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000547 AC: 80 AN: 1461888 Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26 AN XY: 727242

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

American (AMR) AF: 0.00177 AC: 79 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: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.000262 AC: 4 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000128

ExAC AF: 0.000239 AC: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.88	T
PhyloP100		6.5
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.31
Sift	Benign	0.23	T
Sift4G	Benign	0.18	T
Polyphen		0.058	B
Vest4		0.43
MutPred		0.43		Loss of disorder (P = 0.0204)
MVP		0.63
MPC		0.20
ClinPred		0.80	D
GERP RS		5.2
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.67
gMVP		0.52
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;