dbSNP rs567008499: DND1:p.Ala157Val (chr5-140672579-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_194249.3(DND1):c.470C>T(p.Ala157Val) variant causes a missense change. The variant allele was found at a frequency of 0.000144 in 1,577,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

DND1
NM_194249.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009754658).

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.470C>T	p.Ala157Val	missense	Exon 3 of 4	NP_919225.1	Q8IYX4
	WDR55	NM_017706.5	MANE Select	c.*2925G>A		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.470C>T	p.Ala157Val	missense	Exon 3 of 4	ENSP00000445366.1	Q8IYX4
WDR55	ENST00000504897.2	TSL:2	n.*447G>A		non_coding_transcript_exon	Exon 8 of 8	ENSP00000439719.1	G3V1J0
WDR55	ENST00000504897.2	TSL:2	n.*447G>A		3_prime_UTR	Exon 8 of 8	ENSP00000439719.1	G3V1J0

Frequencies

GnomAD3 genomes

AF:

0.000829

AC:

126

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

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:

0.00

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000185

AC:

AN:

184108

AF XY:

0.000185

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.000301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000128

Gnomad OTH exome

AF:

0.000205

GnomAD4 exome

AF:

0.0000701

AC:

100

AN:

1425668

Hom.:

Cov.:

AF XY:

0.0000438

AC XY:

AN XY:

707780

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

32896

American (AMR)

AF:

0.000411

AC:

AN:

41346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25576

East Asian (EAS)

AF:

0.00

AC:

AN:

38458

South Asian (SAS)

AF:

0.0000477

AC:

AN:

83790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39952

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1100416

Other (OTH)

AF:

0.000152

AC:

AN:

59104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

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

AF:

0.000834

AC:

127

AN:

152190

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00272

AC:

113

AN:

41536

American (AMR)

AF:

0.000784

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67974

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.00103

ExAC

AF:

0.000224

AC:

ClinVar

ClinVar submissions as Germline

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

0.096

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.72

M_CAP

Benign

0.030

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.80

PhyloP100

3.7

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.30

REVEL

Benign

0.066

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.085

Vest4

0.21

MutPred

0.42

Loss of disorder (P = 0.0881)

MVP

0.35

MPC

0.77

ClinPred

0.013

GERP RS

5.0

Varity_R

0.16

gMVP

0.42

Mutation Taster

=93/7

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over