15-52313744-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001382347.1(MYO5A):c.5595C>G(p.Thr1865=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000695 in 1,614,168 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00088 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (9 hom.)
• Consequence: MYO5A NM_001382347.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.89

Genes affected

MYO5A (HGNC:7602): (myosin VA) This gene is one of three myosin V heavy-chain genes, belonging to the myosin gene superfamily. Myosin V is a class of actin-based motor proteins involved in cytoplasmic vesicle transport and anchorage, spindle-pole alignment and mRNA translocation. The protein encoded by this gene is abundant in melanocytes and nerve cells. Mutations in this gene cause Griscelli syndrome type-1 (GS1) and neuroectodermal melanolysosomal disease, or Elejalde disease. [provided by RefSeq, Sep 2023]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 15-52313744-G-C is Benign according to our data. Variant chr15-52313744-G-C is described in ClinVar as [Benign]. Clinvar id is 717952.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-52313744-G-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.89 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00088 (134/152306) while in subpopulation EAS AF= 0.0191 (99/5180). AF 95% confidence interval is 0.0161. There are 3 homozygotes in gnomad4. There are 84 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1	c.5595C>G	p.Thr1865=	synonymous_variant	42/42	ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7	c.5595C>G	p.Thr1865=	synonymous_variant	42/42	5	NM_001382347.1

Frequencies

GnomAD3 genomes AF: 0.000874 AC: 133 AN: 152188 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00168 AC: 418 AN: 249310 Hom.: 2 AF XY: 0.00169 AC XY: 228 AN XY: 135236

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0211

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.000464

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000676 AC: 988 AN: 1461862 Hom.: 9 Cov.: 31 AF XY: 0.000696 AC XY: 506 AN XY: 727230

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0201

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.000618

Gnomad4 NFE exome AF: 0.0000665

Gnomad4 OTH exome AF: 0.000878

GnomAD4 genome AF: 0.000880 AC: 134 AN: 152306 Hom.: 3 Cov.: 33 AF XY: 0.00113 AC XY: 84 AN XY: 74460

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000466 Hom.: 0

Bravo AF: 0.00113

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	5.8
Dann	Benign	0.72

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: rs75355222; hg19: chr15-52605941;