rs148328402

Positions:

chr3-50341912-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

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

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 (HGNC:):

ZMYND10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 241065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-50341912-C-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYND10	NM_015896.4 linkuse as main transcript	c.1019G>A	p.Arg340Gln	missense_variant	10/12	ENST00000231749.8	NP_056980.2	O75800-1
ZMYND10	NM_001308379.2 linkuse as main transcript	c.1004G>A	p.Arg335Gln	missense_variant	9/11		NP_001295308.1	O75800-2
ZMYND10	XM_005265216.4 linkuse as main transcript	c.782G>A	p.Arg261Gln	missense_variant	9/11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8 linkuse as main transcript	c.1019G>A	p.Arg340Gln	missense_variant	10/12	1	NM_015896.4	ENSP00000231749.3		O75800-1

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

GnomAD3 exomes

AF:

0.00281

AC:

706

AN:

251174

Hom.:

AF XY:

0.00281

AC XY:

382

AN XY:

135838

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 SAS exome

AF:

0.00118

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

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.00903

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00147

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.00274

Gnomad4 OTH exome

AF:

0.00341

GnomAD4 genome

AF:

0.00254

AC:

387

AN:

152384

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74526

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00369

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00335

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	ZMYND10: BP4, BS2 -

Primary ciliary dyskinesia 22

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 17, 2021

- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

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

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;.

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

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

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