7-44963109-C-T

Variant names:

• chr7-44963109-C-T
• rs772491166
• NM_033054.3:c.2761G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033054.3(MYO1G):​c.2761G>A​(p.Val921Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000224 in 1,341,020 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: MYO1G NM_033054.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.78

Genes affected

MYO1G (HGNC:13880): (myosin IG) MYO1G is a plasma membrane-associated class I myosin (see MIM 601478) that is abundant in T and B lymphocytes and mast cells (Pierce et al., 2001 [PubMed 11544309]; Patino-Lopez et al., 2010 [PubMed 20071333]).[supplied by OMIM, Jun 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1G	NM_033054.3	c.2761G>A	p.Val921Met	missense_variant	Exon 21 of 22	ENST00000258787.12	NP_149043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1G	ENST00000258787.12	c.2761G>A	p.Val921Met	missense_variant	Exon 21 of 22	1	NM_033054.3	ENSP00000258787.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000224 AC: 3 AN: 1341020 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 660070

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: 0.00000283

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.0000289 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2761G>A (p.V921M) alteration is located in exon 21 (coding exon 21) of the MYO1G gene. This alteration results from a G to A substitution at nucleotide position 2761, causing the valine (V) at amino acid position 921 to be replaced by a methionine (M). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.25
Sift	Benign	0.051	T;.
Sift4G	Uncertain	0.045	D;.
Polyphen		1.0	D;.
Vest4		0.33
MutPred		0.59		Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);
MVP		0.58
MPC		1.1
ClinPred		0.95	D
GERP RS		3.9
Varity_R		0.16
gMVP		0.67

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: rs772491166; hg19: chr7-45002708;