3-50341912-C-T

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.1019G>A(p.Arg340Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,614,188 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. R340W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 20 hom. )

Consequence

ZMYND10
NM_015896.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.60

Publications

8 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=0.0070642233).

BP6

Variant 3-50341912-C-T is Benign according to our data. Variant chr3-50341912-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00254 (387/152384) while in subpopulation NFE AF = 0.00369 (251/68038). AF 95% confidence interval is 0.00331. There are 2 homozygotes in GnomAd4. There are 175 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ZMYND10	NM_015896.4 link	c.1019G>A	p.Arg340Gln	missense_variant	Exon 10 of 12	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2 link	c.1004G>A	p.Arg335Gln	missense_variant	Exon 9 of 11		NP_001295308.1
ZMYND10	XM_005265216.4 link	c.782G>A	p.Arg261Gln	missense_variant	Exon 9 of 11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8 link	c.1019G>A	p.Arg340Gln	missense_variant	Exon 10 of 12	1	NM_015896.4	ENSP00000231749.3

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

387

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00369

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00281

AC:

706

AN:

251174

AF XY:

0.00281

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00855

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00360

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00268

AC:

3918

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

1984

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33476

American (AMR)

AF:

0.00347

AC:

155

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00903

AC:

236

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00147

AC:

127

AN:

86258

European-Finnish (FIN)

AF:

0.00157

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00815

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00274

AC:

3051

AN:

1111982

Other (OTH)

AF:

0.00341

AC:

206

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

276

552

827

1103

1379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<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:

0.00254

AC:

387

AN:

152384

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74526

show subpopulations

African (AFR)

AF:

0.000721

AC:

AN:

41590

American (AMR)

AF:

0.00314

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00124

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000941

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00369

AC:

251

AN:

68038

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00283

Hom.:

Bravo

AF:

0.00296

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00275

AC:

334

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00528

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

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZMYND10: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary ciliary dyskinesia 22

Benign:1

Dec 17, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0071

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

PhyloP100

1.6

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.051

Sift

Benign

0.33

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.010

B;B

Vest4

0.30

MVP

0.072

MPC

0.19

ClinPred

0.0087

GERP RS

4.1

Varity_R

0.075

gMVP

0.24

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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