rs114377074

chr3-50343622-A-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.319-6T>C variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003235
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.33

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=-0.83).
• 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 GnomAd at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND10	NM_015896.4	c.319-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000231749.8
ZMYND10	NM_001308379.2	c.319-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ZMYND10	XM_005265216.4	c.82-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND10	ENST00000231749.8	c.319-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015896.4	P1
ZMYND10-AS1	ENST00000440013.1	n.124-1949A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1939 AN: 152170 Hom.: 47 Cov.: 33

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.: 10 AF XY: 0.00233 AC XY: 317 AN XY: 135870

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.: 33 Cov.: 33 AF XY: 0.00110 AC XY: 803 AN XY: 727224

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.: 47 Cov.: 33 AF XY: 0.0130 AC XY: 965 AN XY: 74466

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.: 7

Bravo AF: 0.0155

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

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	-0.83
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

Other links and lift over

dbSNP: rs114377074; hg19: chr3-50381053;