chr3-50342543-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015896.4(ZMYND10):c.727C>T(p.Arg243Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000898 in 1,613,592 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R243H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 1 hom. )

Consequence

ZMYND10
NM_015896.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.345

Publications

3 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011281699).

BP6

Variant 3-50342543-G-A is Benign according to our data. Variant chr3-50342543-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00316 (481/152296) while in subpopulation AFR AF = 0.00897 (373/41560). AF 95% confidence interval is 0.00822. There are 2 homozygotes in GnomAd4. There are 224 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

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.727C>T	p.Arg243Cys	missense	Exon 8 of 12	NP_056980.2
	ZMYND10	NM_001308379.2		c.712C>T	p.Arg238Cys	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.727C>T	p.Arg243Cys	missense	Exon 8 of 12	ENSP00000231749.3
ZMYND10	ENST00000360165.7	TSL:1	c.712C>T	p.Arg238Cys	missense	Exon 7 of 11	ENSP00000353289.3
ZMYND10	ENST00000442887.1	TSL:1	c.598C>T	p.Arg200Cys	missense	Exon 8 of 9	ENSP00000393687.1

Frequencies

GnomAD3 genomes

AF:

0.00316

AC:

481

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00900

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

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:

0.000603

Gnomad OTH

AF:

0.00957

GnomAD2 exomes

AF:

0.00113

AC:

284

AN:

250592

AF XY:

0.00101

show subpopulations

Gnomad AFR exome

AF:

0.00986

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000539

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000662

AC:

968

AN:

1461296

Hom.:

Cov.:

AF XY:

0.000655

AC XY:

476

AN XY:

726818

show subpopulations

African (AFR)

AF:

0.00843

AC:

282

AN:

33470

American (AMR)

AF:

0.00163

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26112

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000462

AC:

513

AN:

1111566

Other (OTH)

AF:

0.00146

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

120

179

239

299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00316

AC:

481

AN:

152296

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

224

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00897

AC:

373

AN:

41560

American (AMR)

AF:

0.00307

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

68020

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

122

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:

0.00117

Hom.:

Bravo

AF:

0.00377

ESP6500AA

AF:

0.0104

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00133

AC:

161

EpiCase

AF:

0.000927

EpiControl

AF:

0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZMYND10: BP4

Primary ciliary dyskinesia 22

Benign:1

Apr 08, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary ciliary dyskinesia

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.71

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.1

PhyloP100

0.34

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.11

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.011

Polyphen

0.99

Vest4

0.26

MVP

0.030

MPC

0.22

ClinPred

0.036

GERP RS

2.9

Varity_R

0.18

gMVP

0.27

Mutation Taster

=91/9

polymorphism

(source)

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

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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