chr15-35538422-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_080650.4(DPH6):​c.164A>T​(p.His55Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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

8
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.97
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.86

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DPH6NM_080650.4 linkc.164A>T p.His55Leu missense_variant Exon 3 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.164A>T p.His55Leu missense_variant Exon 3 of 9 1 NM_080650.4 ENSP00000256538.4 Q7L8W6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.164A>T (p.H55L) alteration is located in exon 3 (coding exon 3) of the DPH6 gene. This alteration results from a A to T substitution at nucleotide position 164, causing the histidine (H) at amino acid position 55 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
27
DANN
Benign
0.97
DEOGEN2
Benign
0.069
T;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Benign
0.054
D
MetaRNN
Pathogenic
0.86
D;D;D
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.5
M;.;M
PrimateAI
Uncertain
0.63
T
PROVEAN
Pathogenic
-10
D;D;D
REVEL
Uncertain
0.61
Sift
Uncertain
0.0060
D;D;D
Sift4G
Uncertain
0.023
D;.;T
Polyphen
0.98
D;.;.
Vest4
0.90
MutPred
0.59
Loss of phosphorylation at T52 (P = 0.1171);.;Loss of phosphorylation at T52 (P = 0.1171);
MVP
0.58
MPC
0.27
ClinPred
1.0
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.86
gMVP
0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-35830623; API