2-191329939-G-T

Position:

• chr2-191329939-G-T

Variant summary

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

The ENST00000392318.8(MYO1B):​c.256G>T​(p.Ala86Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000618 in 1,457,462 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: MYO1B ENST00000392318.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.99

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, 0.967
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1B	NM_001130158.3	c.256G>T	p.Ala86Ser	missense_variant	4/31	ENST00000392318.8	NP_001123630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1B	ENST00000392318.8	c.256G>T	p.Ala86Ser	missense_variant	4/31	1	NM_001130158.3	ENSP00000376132	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000618 AC: 9 AN: 1457462 Hom.: 0 Cov.: 30 AF XY: 0.00000690 AC XY: 5 AN XY: 725120

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: 0.00000811

Gnomad4 OTH exome AF: 0.00

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

Jul 12, 2023

The c.256G>T (p.A86S) alteration is located in exon 4 (coding exon 3) of the MYO1B gene. This alteration results from a G to T substitution at nucleotide position 256, causing the alanine (A) at amino acid position 86 to be replaced by a serine (S). 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	0.20
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;.;D;D;D;D;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D;.;D;D;D;D
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Benign	2.0	.;M;M;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.8	D;N;N;N;D;D;N
REVEL	Pathogenic	0.77
Sift	Benign	0.048	D;T;T;T;D;D;T
Sift4G	Benign	0.13	T;T;T;T;T;D;T
Polyphen		0.99, 0.99	.;D;D;D;.;.;.
Vest4		0.61, 0.61, 0.61
MutPred		0.89		Gain of disorder (P = 0.0263);Gain of disorder (P = 0.0263);Gain of disorder (P = 0.0263);Gain of disorder (P = 0.0263);Gain of disorder (P = 0.0263);Gain of disorder (P = 0.0263);Gain of disorder (P = 0.0263);
MVP		0.76
MPC		0.33
ClinPred		0.95	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.65

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: rs1456538068; hg19: chr2-192194665;