rs3735485

Positions:

• chr7-44969742-A-G
• chr7-44969742-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033054.3(MYO1G):​c.1466T>C​(p.Met489Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,609,976 control chromosomes in the GnomAD database, including 590,159 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.88 (59002 hom., cov: 32)
  • Exomes 𝑓: 0.85 (531157 hom.)
• Consequence: MYO1G NM_033054.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.551202E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1G	NM_033054.3	c.1466T>C	p.Met489Thr	missense_variant	11/22	ENST00000258787.12	NP_149043.2
MYO1G	XR_007060129.1	n.1520T>C		non_coding_transcript_exon_variant	11/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1G	ENST00000258787.12	c.1466T>C	p.Met489Thr	missense_variant	11/22	1	NM_033054.3	ENSP00000258787	P1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133420 AN: 151598 Hom.: 58947 Cov.: 32

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.827

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.846

GnomAD3 exomes AF: 0.868 AC: 216816 AN: 249864 Hom.: 94362 AF XY: 0.863 AC XY: 116705 AN XY: 135268

Gnomad AFR exome AF: 0.969

Gnomad AMR exome AF: 0.895

Gnomad ASJ exome AF: 0.824

Gnomad EAS exome AF: 0.909

Gnomad SAS exome AF: 0.864

Gnomad FIN exome AF: 0.882

Gnomad NFE exome AF: 0.841

Gnomad OTH exome AF: 0.852

GnomAD4 exome AF: 0.853 AC: 1243681 AN: 1458260 Hom.: 531157 Cov.: 66 AF XY: 0.852 AC XY: 617939 AN XY: 725412

Gnomad4 AFR exome AF: 0.969

Gnomad4 AMR exome AF: 0.892

Gnomad4 ASJ exome AF: 0.822

Gnomad4 EAS exome AF: 0.923

Gnomad4 SAS exome AF: 0.862

Gnomad4 FIN exome AF: 0.882

Gnomad4 NFE exome AF: 0.844

Gnomad4 OTH exome AF: 0.855

GnomAD4 genome AF: 0.880 AC: 133534 AN: 151716 Hom.: 59002 Cov.: 32 AF XY: 0.881 AC XY: 65354 AN XY: 74190

Gnomad4 AFR AF: 0.966

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.845

Alfa AF: 0.849 Hom.: 48003

Bravo AF: 0.887

TwinsUK AF: 0.837 AC: 3103

ALSPAC AF: 0.840 AC: 3237

ESP6500AA AF: 0.963 AC: 4244

ESP6500EA AF: 0.841 AC: 7230

ExAC AF: 0.869 AC: 105422

Asia WGS AF: 0.866 AC: 3010 AN: 3476

EpiCase AF: 0.831

EpiControl AF: 0.832

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.7
DANN	Benign	0.30
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.032	T;T
MetaRNN	Benign	6.6e-7	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.4	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.0	N;.
REVEL	Benign	0.099
Sift	Benign	0.45	T;.
Sift4G	Benign	0.28	T;.
Polyphen		0.0	B;.
Vest4		0.024
MPC		0.40
ClinPred		0.00061	T
GERP RS		4.0
Varity_R		0.059
gMVP		0.093

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: rs3735485; hg19: chr7-45009341; COSMIC: COSV51855269;