chr17-36498522-C-T

Variant names:

• chr17-36498522-C-T
• NM_001163735.2:c.2501G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001163735.2(MYO19):​c.2501G>A​(p.Gly834Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO19 NM_001163735.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.923

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066916674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO19	NM_001163735.2	c.2501G>A	p.Gly834Asp	missense_variant	Exon 25 of 26	ENST00000614623.5	NP_001157207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO19	ENST00000614623.5	c.2501G>A	p.Gly834Asp	missense_variant	Exon 25 of 26	2	NM_001163735.2	ENSP00000479518.1
MYO19	ENST00000610930.4	c.1901G>A	p.Gly634Asp	missense_variant	Exon 21 of 22	5		ENSP00000478437.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2501G>A (p.G834D) alteration is located in exon 25 (coding exon 23) of the MYO19 gene. This alteration results from a G to A substitution at nucleotide position 2501, causing the glycine (G) at amino acid position 834 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.71
DEOGEN2	Benign	0.0067	T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.25	N
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.30	T
Sift4G	Benign	0.97	T;T
Polyphen		0.0	B;B
Vest4		0.20
MutPred		0.40		Loss of MoRF binding (P = 0.1035);.;
MVP		0.061
ClinPred		0.023	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-34854366;