Genetic Variant DND1:p.Leu156Phe (chr5-140672583-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_194249.3(DND1):c.466C>T(p.Leu156Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000697 in 1,577,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

DND1
NM_194249.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.41

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]

DND1 links:

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]

WDR55 links:

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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=0.17415062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DND1	NM_194249.3 link	c.466C>T	p.Leu156Phe	missense_variant	Exon 3 of 4	ENST00000542735.2	NP_919225.1	Q8IYX4
WDR55	NM_017706.5 link	c.*2929G>A		downstream_gene_variant		ENST00000358337.10	NP_060176.3	Q9H6Y2-1
WDR55	XM_005268469.4 link	c.*1351G>A		downstream_gene_variant			XP_005268526.1	Q9H6Y2-1
WDR55	XM_017009600.3 link	c.*2929G>A		downstream_gene_variant			XP_016865089.1	G3V1J0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DND1	ENST00000542735.2 link	c.466C>T	p.Leu156Phe	missense_variant	Exon 3 of 4	1	NM_194249.3	ENSP00000445366.1		Q8IYX4
WDR55	ENST00000358337.10 link	c.*2929G>A		downstream_gene_variant		1	NM_017706.5	ENSP00000351100.5		Q9H6Y2-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152092

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183536

Hom.:

AF XY:

0.00000977

AC XY:

AN XY:

102390

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:

0.00

Gnomad NFE exome

AF:

0.0000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000702

AC:

AN:

1425018

Hom.:

Cov.:

AF XY:

0.00000565

AC XY:

AN XY:

707408

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:

0.00000818

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.018

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.69

M_CAP

Benign

0.026

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.93

REVEL

Benign

0.070

Sift

Benign

0.14

Sift4G

Uncertain

0.050

Polyphen

0.41

Vest4

0.33

MutPred

0.39

Gain of helix (P = 0.0425);

MVP

0.32

MPC

0.96

ClinPred

0.20

GERP RS

5.7

Varity_R

0.23

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over