dbSNP rs3751617: MYO5A:c.*3G>C (chr15-52313693-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001382347.1(MYO5A):c.*3G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 1,614,122 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 6 hom. )

Consequence

MYO5A
NM_001382347.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.62

Publications

1 publications found

Variant links:

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]

MYO5A Gene-Disease associations (from GenCC):

Griscelli syndrome type 1
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
Griscelli syndrome type 3
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MYO5A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 15-52313693-C-G is Benign according to our data. Variant chr15-52313693-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 435920.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000407 (62/152262) while in subpopulation EAS AF = 0.00636 (33/5188). AF 95% confidence interval is 0.00465. There are 2 homozygotes in GnomAd4. There are 34 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382347.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYO5A	NM_001382347.1	MANE Select	c.*3G>C	3_prime_UTR	Exon 42 of 42	NP_001369276.1	Q9Y4I1-3
MYO5A	NM_001382348.1		c.*3G>C	3_prime_UTR	Exon 43 of 43	NP_001369277.1
MYO5A	NM_001382349.1		c.*3G>C	3_prime_UTR	Exon 42 of 42	NP_001369278.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYO5A	ENST00000399233.7	TSL:5 MANE Select	c.*3G>C	3_prime_UTR	Exon 42 of 42	ENSP00000382179.4	Q9Y4I1-3
MYO5A	ENST00000399231.8	TSL:1	c.*3G>C	3_prime_UTR	Exon 41 of 41	ENSP00000382177.3	Q9Y4I1-1
MYO5A	ENST00000356338.11	TSL:1	c.*3G>C	3_prime_UTR	Exon 41 of 41	ENSP00000348693.7	A0A8J8YWI7

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00654

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000890

AC:

222

AN:

249432

AF XY:

0.00103

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00662

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.000588

AC:

860

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000666

AC XY:

484

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0119

AC:

473

AN:

39696

South Asian (SAS)

AF:

0.00362

AC:

312

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112000

Other (OTH)

AF:

0.00119

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000407

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00636

AC:

AN:

5188

South Asian (SAS)

AF:

0.00395

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000122

Hom.:

Bravo

AF:

0.000310

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.1

(source)

DANN

Benign

0.70

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over