17-36497725-C-T

Variant summary

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

The NM_001163735.2(MYO19):c.2757+541G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 184,406 control chromosomes in the GnomAD database, including 655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (628 hom., cov: 32)
  • Exomes 𝑓: 0.038 (27 hom.)
• Consequence: MYO19 NM_001163735.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.303

Genes affected

MYO19 (HGNC:26234): (myosin XIX) Enables actin binding activity. Involved in regulation of cytokinesis and regulation of mitochondrial fission. Acts upstream of or within mitochondrion migration along actin filament. Located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZNHIT3 (HGNC:12309): (zinc finger HIT-type containing 3) Predicted to enable thyroid hormone receptor binding activity. Predicted to be involved in box C/D snoRNP assembly; maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); and snoRNA localization. Located in cytoplasm and nucleus. Implicated in PEHO syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.886575).
• BP6: Variant 17-36497725-C-T is Benign according to our data. Variant chr17-36497725-C-T is described in ClinVar as [Benign]. Clinvar id is 3056481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO19	NM_001163735.2	c.2757+541G>A		intron_variant		ENST00000614623.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO19	ENST00000614623.5	c.2757+541G>A		intron_variant		2	NM_001163735.2	P1

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10642 AN: 152064 Hom.: 628 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0736

GnomAD4 exome AF: 0.0378 AC: 1217 AN: 32224 Hom.: 27 Cov.: 4 AF XY: 0.0378 AC XY: 596 AN XY: 15776

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00971

Gnomad4 EAS exome AF: 0.0224

Gnomad4 SAS exome AF: 0.0116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0360

Gnomad4 OTH exome AF: 0.0362

GnomAD4 genome AF: 0.0701 AC: 10663 AN: 152182 Hom.: 628 Cov.: 32 AF XY: 0.0677 AC XY: 5036 AN XY: 74412

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0474

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.0337

Gnomad4 NFE AF: 0.0357

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0544 Hom.: 34

Bravo AF: 0.0756

ExAC AF: 0.00504 AC: 15

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ZNHIT3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.8
Dann	Benign	0.62
FATHMM_MKL	Benign	0.016	N
MutationTaster	Benign	1.0	P;P;P;P;P
Vest4		0.033
GERP RS		0.23

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: rs140610432; hg19: chr17-34853569;