rs61739531

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-44977022-C-G
• chr7-44977022-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_033054.3(MYO1G):​c.145G>C​(p.Val49Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. V49M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYO1G NM_033054.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.905

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1G	NM_033054.3	c.145G>C	p.Val49Leu	missense_variant	Exon 2 of 22	ENST00000258787.12	NP_149043.2
MYO1G	XR_007060129.1	n.199G>C		non_coding_transcript_exon_variant	Exon 2 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1G	ENST00000258787.12	c.145G>C	p.Val49Leu	missense_variant	Exon 2 of 22	1	NM_033054.3	ENSP00000258787.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461178 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726890

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.3	N;.
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0080	D;.
Sift4G	Uncertain	0.022	D;.
Polyphen		0.92	P;.
Vest4		0.77
MutPred		0.82		Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);
MVP		0.75
MPC		0.95
ClinPred		0.92	D
GERP RS		3.9
Varity_R		0.30
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-45016621;