chr2-191364176-A-G

Position:

• chr2-191364176-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000392318.8(MYO1B):​c.932A>G​(p.Glu311Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO1B ENST00000392318.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.18

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1B	NM_001130158.3	c.932A>G	p.Glu311Gly	missense_variant	11/31	ENST00000392318.8	NP_001123630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1B	ENST00000392318.8	c.932A>G	p.Glu311Gly	missense_variant	11/31	1	NM_001130158.3	ENSP00000376132	P1
MYO1B	ENST00000304164.8	c.932A>G	p.Glu311Gly	missense_variant	11/31	1		ENSP00000306382	P1
MYO1B	ENST00000339514.8	c.932A>G	p.Glu311Gly	missense_variant	11/29	1		ENSP00000341903
MYO1B	ENST00000392316.5	c.932A>G	p.Glu311Gly	missense_variant	10/29	5		ENSP00000376130

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 26, 2024

The c.932A>G (p.E311G) alteration is located in exon 11 (coding exon 10) of the MYO1B gene. This alteration results from a A to G substitution at nucleotide position 932, causing the glutamic acid (E) at amino acid position 311 to be replaced by a glycine (G). 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	Benign	0.15
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	.;D;D;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;.;D;D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	1.7	L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-4.1	D;D;D;D
REVEL	Pathogenic	0.69
Sift	Benign	0.088	T;T;T;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.14	B;B;B;.
Vest4		0.81
MutPred		0.50		Loss of stability (P = 0.0339);Loss of stability (P = 0.0339);Loss of stability (P = 0.0339);Loss of stability (P = 0.0339);
MVP		0.60
MPC		0.64
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.29
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-192228902;