7-44977022-C-T

Variant names:

• chr7-44977022-C-T
• rs61739531
• NM_033054.3:c.145G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033054.3(MYO1G):​c.145G>A​(p.Val49Met) variant causes a missense change. The variant allele was found at a frequency of 0.203 in 1,613,356 control chromosomes in the GnomAD database, including 35,980 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3135 hom., cov: 33)
  • Exomes 𝑓: 0.20 (32845 hom.)
• Consequence: MYO1G NM_033054.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01
• Publications: 26 publications found

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]

ENSG00000308366 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056494176).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033054.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1G	NM_033054.3	MANE Select	c.145G>A	p.Val49Met	missense	Exon 2 of 22	NP_149043.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1G	ENST00000258787.12	TSL:1 MANE Select	c.145G>A	p.Val49Met	missense	Exon 2 of 22	ENSP00000258787.7
	MYO1G	ENST00000495831.5	TSL:1	n.96-365G>A		intron	N/A	ENSP00000417650.1
	MYO1G	ENST00000648014.1		c.145G>A	p.Val49Met	missense	Exon 2 of 21	ENSP00000498184.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29042 AN: 152098 Hom.: 3133 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0939

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.179

GnomAD2 exomes AF: 0.184 AC: 46100 AN: 249892 AF XY: 0.182

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.102

Gnomad FIN exome AF: 0.350

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.204 AC: 298797 AN: 1461140 Hom.: 32845 Cov.: 34 AF XY: 0.200 AC XY: 145383 AN XY: 726880

African (AFR) AF: 0.140 AC: 4692 AN: 33478

American (AMR) AF: 0.153 AC: 6857 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3136 AN: 26134

East Asian (EAS) AF: 0.0750 AC: 2976 AN: 39698

South Asian (SAS) AF: 0.0694 AC: 5983 AN: 86256

European-Finnish (FIN) AF: 0.343 AC: 18085 AN: 52738

Middle Eastern (MID) AF: 0.128 AC: 737 AN: 5766

European-Non Finnish (NFE) AF: 0.220 AC: 244894 AN: 1111966

Other (OTH) AF: 0.189 AC: 11437 AN: 60380

GnomAD4 genome AF: 0.191 AC: 29055 AN: 152216 Hom.: 3135 Cov.: 33 AF XY: 0.195 AC XY: 14488 AN XY: 74418

African (AFR) AF: 0.143 AC: 5947 AN: 41544

American (AMR) AF: 0.167 AC: 2555 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3470

East Asian (EAS) AF: 0.0939 AC: 486 AN: 5174

South Asian (SAS) AF: 0.0711 AC: 343 AN: 4824

European-Finnish (FIN) AF: 0.360 AC: 3819 AN: 10600

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14795 AN: 67996

Other (OTH) AF: 0.177 AC: 373 AN: 2112

Alfa AF: 0.199 Hom.: 4449

Bravo AF: 0.179

TwinsUK AF: 0.215 AC: 797

ALSPAC AF: 0.227 AC: 873

ESP6500AA AF: 0.148 AC: 652

ESP6500EA AF: 0.213 AC: 1829

ExAC AF: 0.182 AC: 22070

Asia WGS AF: 0.0800 AC: 278 AN: 3478

EpiCase AF: 0.212

EpiControl AF: 0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.58
Sift	Benign	0.20	T
Sift4G	Benign	0.20	T
Polyphen		0.99	D
Vest4		0.20
MPC		0.96
ClinPred		0.015	T
GERP RS		3.9
Varity_R		0.10
gMVP		0.76
Mutation Taster		=86/14	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61739531; hg19: chr7-45016621; COSMIC: COSV51853854; COSMIC: COSV51853854;