3-50343823-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_015896.4(ZMYND10):c.229G>A(p.Ala77Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,614,202 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 2 hom. )

Consequence

ZMYND10
NM_015896.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 0.152

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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011636406).

BP6

Variant 3-50343823-C-T is Benign according to our data. Variant chr3-50343823-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 410633.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00127 (194/152338) while in subpopulation NFE AF = 0.00201 (137/68038). AF 95% confidence interval is 0.00174. There are 1 homozygotes in GnomAd4. There are 93 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ZMYND10	NM_015896.4 link	c.229G>A	p.Ala77Thr	missense_variant	Exon 3 of 12	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2 link	c.229G>A	p.Ala77Thr	missense_variant	Exon 3 of 11		NP_001295308.1
ZMYND10	XM_005265216.4 link	c.-9G>A		5_prime_UTR_variant	Exon 2 of 11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8 link	c.229G>A	p.Ala77Thr	missense_variant	Exon 3 of 12	1	NM_015896.4	ENSP00000231749.3

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

193

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00201

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00111

AC:

280

AN:

251440

AF XY:

0.00115

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00176

AC:

2570

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1259

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33480

American (AMR)

AF:

0.000581

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00109

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00381

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00209

AC:

2320

AN:

1111996

Other (OTH)

AF:

0.00161

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

139

279

418

558

697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.00127

AC:

194

AN:

152338

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41568

American (AMR)

AF:

0.00189

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00104

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00201

AC:

137

AN:

68038

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.00157

Hom.:

Bravo

AF:

0.00134

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00116

AC:

141

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00267

EpiControl

AF:

0.00243

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 22

Uncertain:2Benign:1

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 09, 2019

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 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 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ZMYND10-related disorder

Benign:1

May 17, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.0

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.10

T;.;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

N;N;.

PhyloP100

0.15

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.59

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.44

T;T;.

Polyphen

0.0050

B;B;.

Vest4

0.33

MVP

0.16

MPC

0.15

ClinPred

0.0022

GERP RS

-3.9

Varity_R

0.036

gMVP

0.099

Mutation Taster

=92/8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over