rs587621539

Positions:

chr3-50345495-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_015896.4(ZMYND10):c.85T>C(p.Ser29Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000374 in 1,603,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

ZMYND10
NM_015896.4 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.60

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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 3-50345495-A-G is Pathogenic according to our data. Variant chr3-50345495-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 410632.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZMYND10	NM_015896.4 linkuse as main transcript	c.85T>C	p.Ser29Pro	missense_variant	1/12	ENST00000231749.8
ZMYND10	NM_001308379.2 linkuse as main transcript	c.85T>C	p.Ser29Pro	missense_variant	1/11
ZMYND10	XM_005265216.4 linkuse as main transcript	c.-44T>C		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND10	ENST00000231749.8 linkuse as main transcript	c.85T>C	p.Ser29Pro	missense_variant	1/12	1	NM_015896.4	P1	O75800-1
ZMYND10-AS1	ENST00000440013.1 linkuse as main transcript	n.124-76A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

229582

Hom.:

AF XY:

0.00000800

AC XY:

AN XY:

125060

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000300

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000294

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.0000296

AC:

AN:

1451220

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

720798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000160

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000289

Gnomad4 OTH exome

AF:

0.0000667

GnomAD4 genome

AF:

0.000112

AC:

AN:

152380

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2024

This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 29 of the ZMYND10 protein (p.Ser29Pro). This variant is present in population databases (rs587621539, gnomAD 0.006%). This missense change has been observed in individual(s) with primary ciliary dyskinesia and features suggestive of primary ciliary dyskinesia (PMID: 23891469; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 410632). 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 expected to disrupt ZMYND10 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.68

T;T

M_CAP

Uncertain

0.29

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

0.59

N;N

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.050

T;D

Polyphen

1.0

D;D

Vest4

0.57

MVP

0.39

MPC

0.66

ClinPred

0.96

GERP RS

3.9

Varity_R

0.73

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over