9-137564451-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138778.5(DPH7):ā€‹c.932A>Gā€‹(p.Asn311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 32)
Exomes š‘“: 0.000030 ( 0 hom. )

Consequence

DPH7
NM_138778.5 missense

Scores

3
16

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.59
Variant links:
Genes affected
DPH7 (HGNC:25199): (diphthamide biosynthesis 7) Diphthamide is a post-translationally modified histidine residue present in elongation factor 2, and is the target of diphtheria toxin. This gene encodes a protein that contains a WD-40 domain, and is thought to be involved in diphthamide biosynthesis. A similar protein in yeast functions as a methylesterase, converting methylated diphthine to diphthine, which can then undergo amidation to produce diphthamide. [provided by RefSeq, Oct 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.090337485).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DPH7NM_138778.5 linkuse as main transcriptc.932A>G p.Asn311Ser missense_variant 8/9 ENST00000277540.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DPH7ENST00000277540.7 linkuse as main transcriptc.932A>G p.Asn311Ser missense_variant 8/91 NM_138778.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000518
AC:
13
AN:
250778
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135650
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000925
Gnomad NFE exome
AF:
0.0000972
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461304
Hom.:
0
Cov.:
31
AF XY:
0.0000275
AC XY:
20
AN XY:
726912
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000369
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152266
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000711
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.000164
EpiControl
AF:
0.000237

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria providedliterature onlyScience for Life laboratory, Karolinska Institutet-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.072
T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.51
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.090
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.53
N
MutationTaster
Benign
0.51
D
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-2.4
N
REVEL
Benign
0.072
Sift
Uncertain
0.027
D
Sift4G
Benign
0.12
T
Polyphen
0.17
B
Vest4
0.13
MVP
0.36
MPC
0.091
ClinPred
0.071
T
GERP RS
0.28
Varity_R
0.054
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs193920785; hg19: chr9-140458903; COSMIC: COSV53024293; COSMIC: COSV53024293; API