15-35373555-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080650.4(DPH6):​c.716A>C​(p.Tyr239Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

DPH6
NM_080650.4 missense

Scores

5
10
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.60
Variant links:
Genes affected
DPH6 (HGNC:30543): (diphthamine biosynthesis 6) Enables diphthine-ammonia ligase activity. Predicted to be involved in peptidyl-diphthamide biosynthetic process from peptidyl-histidine. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DPH6NM_080650.4 linkc.716A>C p.Tyr239Ser missense_variant Exon 8 of 9 ENST00000256538.9 NP_542381.1 Q7L8W6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DPH6ENST00000256538.9 linkc.716A>C p.Tyr239Ser missense_variant Exon 8 of 9 1 NM_080650.4 ENSP00000256538.4 Q7L8W6-1
DPH6ENST00000560386.5 linkn.166A>C non_coding_transcript_exon_variant Exon 3 of 4 1
DPH6ENST00000558266.5 linkc.344A>C p.Tyr115Ser missense_variant Exon 5 of 6 5 ENSP00000454015.1 H0YNH5
DPH6ENST00000558973.1 linkn.173A>C non_coding_transcript_exon_variant Exon 3 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.69
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
T;T
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.66
D;D
MetaSVM
Benign
-0.55
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-8.3
D;D
REVEL
Uncertain
0.38
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.013
D;D
Polyphen
0.92
P;.
Vest4
0.90
MutPred
0.56
Loss of stability (P = 0.1199);.;
MVP
0.49
MPC
0.62
ClinPred
1.0
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.83
gMVP
0.91

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs745733884; hg19: chr15-35665756; API