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17-36498533-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001163735.2(MYO19):c.2490A>G(p.Lys830=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,612,910 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 56 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 35 hom. )

Consequence

MYO19
NM_001163735.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.23
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-36498533-T-C is Benign according to our data. Variant chr17-36498533-T-C is described in ClinVar as [Benign]. Clinvar id is 785567.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.23 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1983/152362) while in subpopulation AFR AF= 0.0449 (1866/41582). AF 95% confidence interval is 0.0432. There are 56 homozygotes in gnomad4. There are 938 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 56 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYO19NM_001163735.2 linkuse as main transcriptc.2490A>G p.Lys830= synonymous_variant 25/26 ENST00000614623.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYO19ENST00000614623.5 linkuse as main transcriptc.2490A>G p.Lys830= synonymous_variant 25/262 NM_001163735.2 P1Q96H55-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0130
AC:
1983
AN:
152244
Hom.:
56
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0450
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00497
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00368
AC:
916
AN:
248682
Hom.:
24
AF XY:
0.00285
AC XY:
385
AN XY:
134984
show subpopulations
Gnomad AFR exome
AF:
0.0506
Gnomad AMR exome
AF:
0.00238
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000373
Gnomad OTH exome
AF:
0.000828
GnomAD4 exome
AF:
0.00147
AC:
2143
AN:
1460548
Hom.:
35
Cov.:
32
AF XY:
0.00134
AC XY:
975
AN XY:
726280
show subpopulations
Gnomad4 AFR exome
AF:
0.0477
Gnomad4 AMR exome
AF:
0.00295
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000194
Gnomad4 OTH exome
AF:
0.00307
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0130
AC:
1983
AN:
152362
Hom.:
56
Cov.:
32
AF XY:
0.0126
AC XY:
938
AN XY:
74518
show subpopulations
Gnomad4 AFR
AF:
0.0449
Gnomad4 AMR
AF:
0.00496
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00622
Hom.:
9
Bravo
AF:
0.0151
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.000491
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
Cadd
Benign
7.3
Dann
Benign
0.69
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs113036400; hg19: chr17-34854377; API