3-50341197-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.*213T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 653,344 control chromosomes in the GnomAD database, including 8,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (2767 hom., cov: 33)
  • Exomes 𝑓: 0.061 (6204 hom.)
• Consequence: ZMYND10 NM_015896.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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=-0.82).
• BP6: Variant 3-50341197-A-G is Benign according to our data. Variant chr3-50341197-A-G is described in ClinVar as [Benign]. Clinvar id is 1221244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND10	NM_015896.4	c.*213T>C		3_prime_UTR_variant	12/12	ENST00000231749.8
ZMYND10	NM_001308379.2	c.*213T>C		3_prime_UTR_variant	11/11
ZMYND10	XM_005265216.4	c.*213T>C		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND10	ENST00000231749.8	c.*213T>C		3_prime_UTR_variant	12/12	1	NM_015896.4	P1
ZMYND10-AS1	ENST00000440013.1	n.92A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18061 AN: 152118 Hom.: 2761 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00375

Gnomad OTH AF: 0.0994

GnomAD4 exome AF: 0.0615 AC: 30816 AN: 501108 Hom.: 6204 Cov.: 6 AF XY: 0.0566 AC XY: 14846 AN XY: 262152

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.00406

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.0115

Gnomad4 FIN exome AF: 0.0451

Gnomad4 NFE exome AF: 0.00322

Gnomad4 OTH exome AF: 0.0720

GnomAD4 genome AF: 0.119 AC: 18123 AN: 152236 Hom.: 2767 Cov.: 33 AF XY: 0.125 AC XY: 9289 AN XY: 74444

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.0216

Gnomad4 FIN AF: 0.0469

Gnomad4 NFE AF: 0.00375

Gnomad4 OTH AF: 0.0998

Alfa AF: 0.0356 Hom.: 687

Bravo AF: 0.147

Asia WGS AF: 0.215 AC: 745 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.55
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3213621; hg19: chr3-50378628;