Genetic Variant NM_194249.3:c.460C>A (chr5-140672589-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_194249.3(DND1):c.460C>A(p.Leu154Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000702 in 1,423,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

DND1
NM_194249.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194249.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DND1	NM_194249.3	MANE Select	c.460C>A	p.Leu154Met	missense	Exon 3 of 4	NP_919225.1	Q8IYX4
	WDR55	NM_017706.5	MANE Select	c.*2935G>T		downstream_gene	N/A	NP_060176.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DND1	ENST00000542735.2	TSL:1 MANE Select	c.460C>A	p.Leu154Met	missense	Exon 3 of 4	ENSP00000445366.1	Q8IYX4
WDR55	ENST00000504897.2	TSL:2	n.*457G>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000439719.1	G3V1J0
WDR55	ENST00000504897.2	TSL:2	n.*457G>T		3_prime_UTR	Exon 8 of 8	ENSP00000439719.1	G3V1J0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000166

AC:

AN:

180772

AF XY:

0.0000199

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000392

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000702

AC:

AN:

1423994

Hom.:

Cov.:

AF XY:

0.00000990

AC XY:

AN XY:

706952

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32914

American (AMR)

AF:

0.00

AC:

AN:

41128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25558

East Asian (EAS)

AF:

0.00

AC:

AN:

38342

South Asian (SAS)

AF:

0.00

AC:

AN:

83578

European-Finnish (FIN)

AF:

0.0000254

AC:

AN:

39408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00000818

AC:

AN:

1099868

Other (OTH)

AF:

0.00

AC:

AN:

59064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000893

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.57

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.54

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.4

PhyloP100

1.4

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.4

REVEL

Benign

0.17

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.56

MutPred

0.41

Loss of helix (P = 0.2022)

MVP

0.42

MPC

1.7

ClinPred

0.68

GERP RS

2.9

Varity_R

0.47

gMVP

0.80

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over