Variant 3-50343153-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_015896.4(ZMYND10):c.564C>G(p.Leu188Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,614,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00090 ( 0 hom. )

Consequence

ZMYND10
NM_015896.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.150

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 -15 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 3-50343153-G-C is Benign according to our data. Variant chr3-50343153-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 525470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000899 (1314/1461882) while in subpopulation NFE AF= 0.0011 (1218/1112002). AF 95% confidence interval is 0.00104. There are 0 homozygotes in gnomad4_exome. There are 623 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYND10	NM_015896.4 linkuse as main transcript	c.564C>G	p.Leu188Leu	synonymous_variant	6/12	ENST00000231749.8	NP_056980.2	O75800-1
ZMYND10	NM_001308379.2 linkuse as main transcript	c.564C>G	p.Leu188Leu	synonymous_variant	6/11		NP_001295308.1	O75800-2
ZMYND10	XM_005265216.4 linkuse as main transcript	c.327C>G	p.Leu109Leu	synonymous_variant	5/11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8 linkuse as main transcript	c.564C>G	p.Leu188Leu	synonymous_variant	6/12	1	NM_015896.4	ENSP00000231749.3		O75800-1

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000545

AC:

137

AN:

251414

Hom.:

AF XY:

0.000522

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.000958

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000899

AC:

1314

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000857

AC XY:

623

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000580

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.000558

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000323

Hom.:

Bravo

AF:

0.000548

EpiCase

AF:

0.000927

EpiControl

AF:

0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Primary ciliary dyskinesia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.8

DANN

Benign

0.73

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