5-140671404-A-T

Variant summary

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

The NM_194249.3(DND1):​c.951T>A​(p.His317Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

DND1
NM_194249.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.563
Variant links:
Genes affected
DND1 (HGNC:23799): (DND microRNA-mediated repression inhibitor 1) This gene encodes a protein that binds to microRNA-targeting sequences of mRNAs, inhibiting microRNA-mediated repression. Reduced expression of this gene has been implicated in tongue squamous cell carcinoma. Two pseudogenes of this gene are located on the long arm of chromosome 17. [provided by RefSeq, Dec 2010]
WDR55 (HGNC:25971): (WD repeat domain 55) Predicted to be involved in rRNA processing. 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23425236).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DND1NM_194249.3 linkc.951T>A p.His317Gln missense_variant 4/4 ENST00000542735.2 NP_919225.1 Q8IYX4
WDR55NM_017706.5 linkc.*1750A>T 3_prime_UTR_variant 7/7 ENST00000358337.10 NP_060176.3 Q9H6Y2-1
WDR55XM_005268469.4 linkc.*172A>T 3_prime_UTR_variant 8/8 XP_005268526.1 Q9H6Y2-1
WDR55XM_017009600.3 linkc.*1750A>T 3_prime_UTR_variant 8/8 XP_016865089.1 G3V1J0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DND1ENST00000542735.2 linkc.951T>A p.His317Gln missense_variant 4/41 NM_194249.3 ENSP00000445366.1 Q8IYX4
WDR55ENST00000358337.10 linkc.*1750A>T 3_prime_UTR_variant 7/71 NM_017706.5 ENSP00000351100.5 Q9H6Y2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 18, 2022The c.951T>A (p.H317Q) alteration is located in exon 4 (coding exon 4) of the DND1 gene. This alteration results from a T to A substitution at nucleotide position 951, causing the histidine (H) at amino acid position 317 to be replaced by a glutamine (Q). 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
Uncertain
0.45
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.099
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.95
N
REVEL
Benign
0.15
Sift
Benign
0.24
T
Sift4G
Benign
0.24
T
Polyphen
0.99
D
Vest4
0.37
MutPred
0.22
Gain of solvent accessibility (P = 0.0338);
MVP
0.56
MPC
1.1
ClinPred
0.48
T
GERP RS
-0.36
Varity_R
0.13
gMVP
0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-140050989; API