chr2-191296145-C-T

Position:

• chr2-191296145-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_Strong BS2

The ENST00000392318.8(MYO1B):​c.170C>T​(p.Pro57Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,454,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: MYO1B ENST00000392318.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.64

Genes affected

MYO1B (HGNC:7596): (myosin IB) Enables ATP binding activity; actin filament binding activity; and microfilament motor activity. Involved in actin filament organization and post-Golgi vesicle-mediated transport. Located in several cellular components, including actin filament; endosome; and perinuclear region of cytoplasm. Colocalizes with trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.993
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1B	NM_001130158.3	c.170C>T	p.Pro57Leu	missense_variant	3/31	ENST00000392318.8	NP_001123630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1B	ENST00000392318.8	c.170C>T	p.Pro57Leu	missense_variant	3/31	1	NM_001130158.3	ENSP00000376132	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000756 AC: 11 AN: 1454602 Hom.: 0 Cov.: 28 AF XY: 0.00000691 AC XY: 5 AN XY: 723736

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000903

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2023

The c.170C>T (p.P57L) alteration is located in exon 3 (coding exon 2) of the MYO1B gene. This alteration results from a C to T substitution at nucleotide position 170, causing the proline (P) at amino acid position 57 to be replaced by a leucine (L). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D;.;D;D;D;D;D;.
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;.;D;D;D;D;D
M_CAP	Pathogenic	0.71	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.7	.;H;H;H;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-9.6	D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.94
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D;D;D
Polyphen		1.0	.;D;D;D;.;.;.;.
Vest4		0.95, 0.96, 0.95
MutPred		0.97		Loss of phosphorylation at S60 (P = 0.1264);Loss of phosphorylation at S60 (P = 0.1264);Loss of phosphorylation at S60 (P = 0.1264);Loss of phosphorylation at S60 (P = 0.1264);Loss of phosphorylation at S60 (P = 0.1264);Loss of phosphorylation at S60 (P = 0.1264);Loss of phosphorylation at S60 (P = 0.1264);Loss of phosphorylation at S60 (P = 0.1264);
MVP		0.92
MPC		1.1
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.93

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

Other links and lift over

dbSNP: rs1688970086; hg19: chr2-192160871;