3-50343153-G-C

Variant names:

• chr3-50343153-G-C
• rs144295551
• NM_015896.4:c.564C>G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_015896.4(ZMYND10):​c.564C>G​(p.Leu188Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,614,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00090 (0 hom.)
• Consequence: ZMYND10 NM_015896.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.150

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 -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 3-50343153-G-C is Benign according to our data. Variant chr3-50343153-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 525470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.15 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000899 (1314/1461882) while in subpopulation NFE AF= 0.0011 (1218/1112002). AF 95% confidence interval is 0.00104. There are 0 homozygotes in gnomad4_exome. There are 623 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND10	NM_015896.4	c.564C>G	p.Leu188Leu	synonymous_variant	Exon 6 of 12	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2	c.564C>G	p.Leu188Leu	synonymous_variant	Exon 6 of 11		NP_001295308.1
ZMYND10	XM_005265216.4	c.327C>G	p.Leu109Leu	synonymous_variant	Exon 5 of 11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8	c.564C>G	p.Leu188Leu	synonymous_variant	Exon 6 of 12	1	NM_015896.4	ENSP00000231749.3

Frequencies

GnomAD3 genomes AF: 0.000558 AC: 85 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000545 AC: 137 AN: 251414 Hom.: 0 AF XY: 0.000522 AC XY: 71 AN XY: 135890

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.000958

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000899 AC: 1314 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.000857 AC XY: 623 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.000580

Gnomad4 NFE exome AF: 0.00110

Gnomad4 OTH exome AF: 0.000878

GnomAD4 genome AF: 0.000558 AC: 85 AN: 152360 Hom.: 0 Cov.: 33 AF XY: 0.000456 AC XY: 34 AN XY: 74514

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000323 Hom.: 0

Bravo AF: 0.000548

EpiCase AF: 0.000927

EpiControl AF: 0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Jun 23, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Primary ciliary dyskinesia Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.8
DANN	Benign	0.73

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: rs144295551; hg19: chr3-50380584; COSMIC: COSV99206307; COSMIC: COSV99206307;