3-50341515-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015896.4(ZMYND10):c.1248-30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,614,102 control chromosomes in the GnomAD database, including 28,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (4251 hom., cov: 33)
  • Exomes 𝑓: 0.15 (24186 hom.)
• Consequence: ZMYND10 NM_015896.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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=-0.81).
• BP6: Variant 3-50341515-A-G is Benign according to our data. Variant chr3-50341515-A-G is described in ClinVar as [Benign]. Clinvar id is 1231903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND10	NM_015896.4	c.1248-30T>C		intron_variant		ENST00000231749.8
ZMYND10	NM_001308379.2	c.1233-30T>C		intron_variant
ZMYND10	XM_005265216.4	c.1011-30T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND10	ENST00000231749.8	c.1248-30T>C		intron_variant		1	NM_015896.4	P1
ZMYND10-AS1	ENST00000440013.1	n.123+287A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30644 AN: 152122 Hom.: 4241 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.188

GnomAD3 exomes AF: 0.223 AC: 56025 AN: 251414 Hom.: 10633 AF XY: 0.202 AC XY: 27433 AN XY: 135886

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.489

Gnomad ASJ exome AF: 0.0783

Gnomad EAS exome AF: 0.678

Gnomad SAS exome AF: 0.116

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.147 AC: 214665 AN: 1461862 Hom.: 24186 Cov.: 33 AF XY: 0.144 AC XY: 104539 AN XY: 727236

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.0801

Gnomad4 EAS exome AF: 0.612

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.202 AC: 30708 AN: 152240 Hom.: 4251 Cov.: 33 AF XY: 0.208 AC XY: 15472 AN XY: 74436

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.192

Alfa AF: 0.155 Hom.: 590

Bravo AF: 0.223

Asia WGS AF: 0.317 AC: 1101 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.7
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1989839; hg19: chr3-50378946; COSMIC: COSV51602574; COSMIC: COSV51602574;