chr3-50341276-C-A

Position:

• chr3-50341276-C-A

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.*134G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,128,220 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (41 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (35 hom.)
• Consequence: ZMYND10 NM_015896.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.137

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=-0.74).
• BP6: Variant 3-50341276-C-A is Benign according to our data. Variant chr3-50341276-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1193297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (2242/152330) while in subpopulation AFR AF= 0.0511 (2125/41578). AF 95% confidence interval is 0.0493. There are 41 homozygotes in gnomad4. There are 1037 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND10	NM_015896.4	c.*134G>T		3_prime_UTR_variant	12/12	ENST00000231749.8
ZMYND10	NM_001308379.2	c.*134G>T		3_prime_UTR_variant	11/11
ZMYND10	XM_005265216.4	c.*134G>T		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND10	ENST00000231749.8	c.*134G>T		3_prime_UTR_variant	12/12	1	NM_015896.4	P1
ZMYND10-AS1	ENST00000440013.1	n.123+48C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2208 AN: 152212 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00163 AC: 1590 AN: 975890 Hom.: 35 Cov.: 13 AF XY: 0.00148 AC XY: 727 AN XY: 491312

Gnomad4 AFR exome AF: 0.0507

Gnomad4 AMR exome AF: 0.00380

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000293

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000929

Gnomad4 OTH exome AF: 0.00421

GnomAD4 genome AF: 0.0147 AC: 2242 AN: 152330 Hom.: 41 Cov.: 33 AF XY: 0.0139 AC XY: 1037 AN XY: 74488

Gnomad4 AFR AF: 0.0511

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00165 Hom.: 0

Bravo AF: 0.0172

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.2
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs112780151; hg19: chr3-50378707;