12-57029584-A-T

Variant names:

• chr12-57029584-A-T
• NM_005379.4:c.2728T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005379.4(MYO1A):​c.2728T>A​(p.Ser910Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYO1A NM_005379.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

Genes affected

MYO1A (HGNC:7595): (myosin IA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09998837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.2728T>A	p.Ser910Thr	missense_variant	Exon 26 of 28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.2728T>A	p.Ser910Thr	missense_variant	Exon 27 of 29		NP_001242970.1
MYO1A	XM_047428876.1	c.2728T>A	p.Ser910Thr	missense_variant	Exon 27 of 29		XP_047284832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.2728T>A	p.Ser910Thr	missense_variant	Exon 26 of 28	1	NM_005379.4	ENSP00000300119.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.039	T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.58	.;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.94	N;N
REVEL	Benign	0.12
Sift	Benign	0.73	T;T
Sift4G	Benign	0.90	T;T
Polyphen		0.13	B;B
Vest4		0.18
MutPred		0.55		Loss of phosphorylation at S910 (P = 0.072);Loss of phosphorylation at S910 (P = 0.072);
MVP		0.46
MPC		0.087
ClinPred		0.59	D
GERP RS		3.3
Varity_R		0.059
gMVP		0.22

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-57423368;