Variant rs114377074 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015896.4(ZMYND10):c.319-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,614,134 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 47 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 33 hom. )

Consequence

ZMYND10
NM_015896.4 splice_region, intron

Scores

Splicing: ADA: 0.00003235

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.33

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:):

ZMYND10-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-50343622-A-G is Benign according to our data. Variant chr3-50343622-A-G is described in ClinVar as [Benign]. Clinvar id is 241068.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1940/152288) while in subpopulation AFR AF= 0.0443 (1841/41542). AF 95% confidence interval is 0.0426. There are 47 homozygotes in gnomad4. There are 965 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ZMYND10	NM_015896.4 linkuse as main transcript	c.319-6T>C	splice_region_variant, intron_variant	ENST00000231749.8	NP_056980.2	O75800-1
ZMYND10	NM_001308379.2 linkuse as main transcript	c.319-6T>C	splice_region_variant, intron_variant		NP_001295308.1	O75800-2
ZMYND10	XM_005265216.4 linkuse as main transcript	c.82-6T>C	splice_region_variant, intron_variant		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8 linkuse as main transcript	c.319-6T>C		splice_region_variant, intron_variant		1	NM_015896.4	ENSP00000231749.3		O75800-1

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1939

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0444

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

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:

0.00669

GnomAD3 exomes

AF:

0.00325

AC:

818

AN:

251354

Hom.:

AF XY:

0.00233

AC XY:

317

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0460

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00132

AC:

1924

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

803

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0486

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00288

GnomAD4 genome

AF:

0.0127

AC:

1940

AN:

152288

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

965

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0443

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00676

Hom.:

Bravo

AF:

0.0155

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.8

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000032

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.0

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