7-44963052-C-A

Variant names:

• chr7-44963052-C-A
• rs749646679
• NM_033054.3:c.2818G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033054.3(MYO1G):​c.2818G>T​(p.Val940Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,525,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V940M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: MYO1G NM_033054.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3238079).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1G	NM_033054.3	MANE Select	c.2818G>T	p.Val940Leu	missense	Exon 21 of 22	NP_149043.2	B0I1T2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1G	ENST00000258787.12	TSL:1 MANE Select	c.2818G>T	p.Val940Leu	missense	Exon 21 of 22	ENSP00000258787.7	B0I1T2-1
	MYO1G	ENST00000495831.5	TSL:1	n.*2480G>T		non_coding_transcript_exon	Exon 20 of 21	ENSP00000417650.1	F8WAS7
	MYO1G	ENST00000495831.5	TSL:1	n.*2480G>T		3_prime_UTR	Exon 20 of 21	ENSP00000417650.1	F8WAS7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1373006 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 677854

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29298

American (AMR) AF: 0.00 AC: 0 AN: 34392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24324

East Asian (EAS) AF: 0.00 AC: 0 AN: 34262

South Asian (SAS) AF: 0.00 AC: 0 AN: 78278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4748

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1073446

Other (OTH) AF: 0.00 AC: 0 AN: 57266

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.077
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.54
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.050
Sift	Benign	0.056	T
Sift4G	Benign	0.10	T
Polyphen		0.35	B
Vest4		0.086
MutPred		0.71		Gain of disorder (P = 0.3859)
MVP		0.47
MPC		1.1
ClinPred		0.78	D
GERP RS		3.9
Varity_R		0.15
gMVP		0.49
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs749646679; hg19: chr7-45002651;