NM_001080779.2:c.3122C>G

Variant names:

• chr17-1467285-G-C
• rs750729307
• NM_001080779.2:c.3122C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_001080779.2(MYO1C):​c.3122C>G​(p.Ser1041Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYO1C NM_001080779.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.36

Genes affected

MYO1C (HGNC:7597): (myosin IC) This gene encodes a member of the unconventional myosin protein family, which are actin-based molecular motors. The protein is found in the cytoplasm, and one isoform with a unique N-terminus is also found in the nucleus. The nuclear isoform associates with RNA polymerase I and II and functions in transcription initiation. The mouse ortholog of this protein also functions in intracellular vesicle transport to the plasma membrane. Multiple transcript variants encoding different isoforms have been found for this gene. The related gene myosin IE has been referred to as myosin IC in the literature, but it is a distinct locus on chromosome 19. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity MYO1C_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1C	NM_001080779.2	c.3122C>G	p.Ser1041Trp	missense_variant	Exon 31 of 32	ENST00000648651.1	NP_001074248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1C	ENST00000648651.1	c.3122C>G	p.Ser1041Trp	missense_variant	Exon 31 of 32		NM_001080779.2	ENSP00000496954.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	.;.;.;D;D;.;.;.;T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	.;D;.;.;D;.;.;D;D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.6	.;.;.;M;M;.;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.8	.;D;.;.;D;D;.;.;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0050	.;D;.;.;D;D;.;.;D
Sift4G	Uncertain	0.0040	.;D;D;.;D;D;.;.;D
Polyphen		1.0	D;D;.;D;D;.;.;.;.
Vest4		0.79, 0.77, 0.77, 0.77
MutPred		0.62		.;.;.;Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);.;.;.;.;
MVP		0.80
MPC		0.78
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.38

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: rs750729307; hg19: chr17-1370579;