Variant 3-50343299-C-G 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.510+8G>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 0.00172 in 1,612,200 control chromosomes in the GnomAD database, including 11 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 11 hom. )

Consequence

ZMYND10
NM_015896.4 splice_region, intron

Scores

Splicing: ADA: 0.0001123

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.438

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 3-50343299-C-G is Benign according to our data. Variant chr3-50343299-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 416259.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00117 (178/152332) while in subpopulation NFE AF= 0.0019 (129/68028). AF 95% confidence interval is 0.00163. There are 0 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ZMYND10	NM_015896.4 linkuse as main transcript	c.510+8G>C	splice_region_variant, intron_variant	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2 linkuse as main transcript	c.510+8G>C	splice_region_variant, intron_variant		NP_001295308.1
ZMYND10	XM_005265216.4 linkuse as main transcript	c.273+8G>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.510+8G>C		splice_region_variant, intron_variant		1	NM_015896.4	ENSP00000231749	P1	O75800-1
ZMYND10-AS1	ENST00000440013.1 linkuse as main transcript	n.123+2071C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

178

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00111

AC:

277

AN:

248964

Hom.:

AF XY:

0.00114

AC XY:

153

AN XY:

134504

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000727

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.00173

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00178

AC:

2601

AN:

1459868

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1267

AN XY:

726120

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000829

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.000132

Gnomad4 NFE exome

AF:

0.00211

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00117

AC:

178

AN:

152332

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.00132

EpiCase

AF:

0.00153

EpiControl

AF:

0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Likely 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

-0.76

CADD

Benign

7.9

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0

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