chr3-50342044-G-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.970C>A(p.Pro324Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,614,204 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 21 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 21 hom. )

Consequence

ZMYND10
NM_015896.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.48

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040352643).

BP6

Variant 3-50342044-G-T is Benign according to our data. Variant chr3-50342044-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241073.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 = 0.00967 (1474/152358) while in subpopulation AFR AF = 0.0338 (1407/41592). AF 95% confidence interval is 0.0324. There are 21 homozygotes in GnomAd4. There are 733 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND10	NM_015896.4 link	c.970C>A	p.Pro324Thr	missense_variant	Exon 9 of 12	ENST00000231749.8	NP_056980.2	O75800-1
ZMYND10	NM_001308379.2 link	c.955C>A	p.Pro319Thr	missense_variant	Exon 8 of 11		NP_001295308.1	O75800-2
ZMYND10	XM_005265216.4 link	c.733C>A	p.Pro245Thr	missense_variant	Exon 8 of 11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8 link	c.970C>A	p.Pro324Thr	missense_variant	Exon 9 of 12	1	NM_015896.4	ENSP00000231749.3		O75800-1

Frequencies

GnomAD3 genomes

AF:

0.00968

AC:

1473

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00243

AC:

611

AN:

251350

AF XY:

0.00171

show subpopulations

Gnomad AFR exome

AF:

0.0348

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00101

AC:

1481

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000844

AC XY:

614

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0376

AC:

1259

AN:

33474

American (AMR)

AF:

0.00125

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000162

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111998

Other (OTH)

AF:

0.00215

AC:

130

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

184

275

367

459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.00967

AC:

1474

AN:

152358

Hom.:

Cov.:

AF XY:

0.00984

AC XY:

733

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0338

AC:

1407

AN:

41592

American (AMR)

AF:

0.00320

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68038

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

142

212

283

354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00349

Hom.:

Bravo

AF:

0.0115

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0343

AC:

151

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00320

AC:

389

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 15, 2023

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary ciliary dyskinesia

Benign:1

Jan 27, 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

0.060

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.19

T;.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.;.

PhyloP100

1.5

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Benign

0.063

Sift

Benign

0.036

D;D;D

Sift4G

Uncertain

0.053

T;D;.

Polyphen

0.0040

B;B;.

Vest4

0.053

MVP

0.067

MPC

0.18

ClinPred

0.016

GERP RS

-1.7

Varity_R

0.11

gMVP

0.44

Mutation Taster

=96/4

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