rs587682566

Variant names:

Variant summary

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

The NM_015896.4(ZMYND10):c.848G>A(p.Ser283Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,596,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

ZMYND10
NM_015896.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.627

Publications

2 publications found

Variant links:

Genes affected

ZMYND10 (HGNC:19412): (zinc finger MYND-type containing 10) This gene encodes a protein containing a MYND-type zinc finger domain that likely functions in assembly of the dynein motor. Mutations in this gene can cause primary ciliary dyskinesia. This gene is also considered a tumor suppressor gene and is often mutated, deleted, or hypermethylated and silenced in cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

ZMYND10 links:

ZMYND10-AS1 (HGNC:40890): (ZMYND10 antisense RNA 1)

ZMYND10-AS1 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=0.03961572).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015896.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYND10	NM_015896.4	MANE Select	c.848G>A	p.Ser283Asn	missense	Exon 8 of 12	NP_056980.2
	ZMYND10	NM_001308379.2		c.833G>A	p.Ser278Asn	missense	Exon 7 of 11	NP_001295308.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZMYND10	ENST00000231749.8	TSL:1 MANE Select	c.848G>A	p.Ser283Asn	missense	Exon 8 of 12	ENSP00000231749.3
ZMYND10	ENST00000360165.7	TSL:1	c.833G>A	p.Ser278Asn	missense	Exon 7 of 11	ENSP00000353289.3
ZMYND10	ENST00000442887.1	TSL:1	c.719G>A	p.Ser240Asn	missense	Exon 8 of 9	ENSP00000393687.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000404

AC:

AN:

222998

AF XY:

0.0000249

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000626

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000426

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000194

AC:

AN:

1444186

Hom.:

Cov.:

AF XY:

0.0000181

AC XY:

AN XY:

717040

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33008

American (AMR)

AF:

0.0000472

AC:

AN:

42392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25818

East Asian (EAS)

AF:

0.000284

AC:

AN:

38708

South Asian (SAS)

AF:

0.00

AC:

AN:

84008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102612

Other (OTH)

AF:

0.000235

AC:

AN:

59692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.0000263

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41480

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67950

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.000142

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Sep 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 283 of the ZMYND10 protein (p.Ser283Asn). This variant is present in population databases (rs587682566, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with ZMYND10-related conditions. ClinVar contains an entry for this variant (Variation ID: 454843). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ZMYND10 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.12

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.61

M_CAP

Benign

0.0079

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.68

PhyloP100

0.63

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

REVEL

Benign

0.14

Sift

Benign

0.27

Sift4G

Benign

0.29

Polyphen

0.0020

Vest4

0.14

MutPred

0.42

Gain of relative solvent accessibility (P = 0.09)

MVP

0.12

MPC

0.15

ClinPred

0.017

GERP RS

4.0

Varity_R

0.12

gMVP

0.10

Mutation Taster

=87/13

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over