rs201732355

chr3-50343299-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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

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-AS1 (HGNC:40890): (ZMYND10 antisense RNA 1)

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND10	NM_015896.4	c.510+8G>C		splice_region_variant, intron_variant		ENST00000231749.8
ZMYND10	NM_001308379.2	c.510+8G>C		splice_region_variant, intron_variant
ZMYND10	XM_005265216.4	c.273+8G>C		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND10	ENST00000231749.8	c.510+8G>C		splice_region_variant, intron_variant		1	NM_015896.4	P1
ZMYND10-AS1	ENST00000440013.1	n.123+2071C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 178 AN: 152214 Hom.: 0 Cov.: 33

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.: 4 AF XY: 0.00114 AC XY: 153 AN XY: 134504

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.: 11 Cov.: 33 AF XY: 0.00174 AC XY: 1267 AN XY: 726120

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.: 0 Cov.: 33 AF XY: 0.000953 AC XY: 71 AN XY: 74486

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.: 0

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

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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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

Other links and lift over

dbSNP: rs201732355; hg19: chr3-50380730;