rs200048542

chr17-1483016-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001080779.2(MYO1C):c.391C>T(p.Arg131Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,611,726 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R131H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00037 (1 hom.)
• Consequence: MYO1C NM_001080779.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.23

Genes affected

MYO1C (HGNC:7597): (myosin IC) This gene encodes a member of the unconventional myosin protein family, which are actin-based molecular motors. The protein is found in the cytoplasm, and one isoform with a unique N-terminus is also found in the nucleus. The nuclear isoform associates with RNA polymerase I and II and functions in transcription initiation. The mouse ortholog of this protein also functions in intracellular vesicle transport to the plasma membrane. Multiple transcript variants encoding different isoforms have been found for this gene. The related gene myosin IE has been referred to as myosin IC in the literature, but it is a distinct locus on chromosome 19. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0200696).
• BP6: Variant 17-1483016-G-A is Benign according to our data. Variant chr17-1483016-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 221916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1C	NM_001080779.2	c.391C>T	p.Arg131Cys	missense_variant	4/32	ENST00000648651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1C	ENST00000648651.1	c.391C>T	p.Arg131Cys	missense_variant	4/32		NM_001080779.2

Frequencies

GnomAD3 genomes AF: 0.000441 AC: 67 AN: 152032 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000473 AC: 117 AN: 247110 Hom.: 0 AF XY: 0.000566 AC XY: 76 AN XY: 134286

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00350

Gnomad NFE exome AF: 0.000306

Gnomad OTH exome AF: 0.000663

GnomAD4 exome AF: 0.000372 AC: 543 AN: 1459694 Hom.: 1 Cov.: 39 AF XY: 0.000369 AC XY: 268 AN XY: 726200

Gnomad4 AFR exome AF: 0.0000897

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00292

Gnomad4 NFE exome AF: 0.000338

Gnomad4 OTH exome AF: 0.000133

GnomAD4 genome AF: 0.000441 AC: 67 AN: 152032 Hom.: 0 Cov.: 31 AF XY: 0.000566 AC XY: 42 AN XY: 74260

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00301

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000438 Hom.: 0

Bravo AF: 0.000174

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000478 AC: 58

EpiCase AF: 0.0000545

EpiControl AF: 0.000297

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anophthalmia-microphthalmia syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Paul Sabatier University EA-4555, Paul Sabatier University

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Pathogenic	0.17
Cadd	Pathogenic	29
Dann	Uncertain	1.0
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.020	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.054	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.78	T
Polyphen		0.99	D;D;.;D;D;.;.;.;.;.;.;.
Vest4		0.76, 0.77, 0.76, 0.77, 0.77
MVP		0.85
MPC		0.77
ClinPred		0.078	T
GERP RS		4.4
Varity_R		0.26
gMVP		0.73

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: rs200048542; hg19: chr17-1386310; COSMIC: COSV100704574; COSMIC: COSV100704574;