12-109393400-A-T

Variant names:

• chr12-109393400-A-T
• rs556070676
• NM_001101421.4:c.244A>T

Variant summary

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

The NM_001101421.4(MYO1H):​c.244A>T​(p.Met82Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,508 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MYO1H NM_001101421.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.84

Genes affected

MYO1H (HGNC:13879): (myosin IH) Predicted to enable actin filament binding activity and microfilament motor activity. Predicted to be involved in actin filament organization and vesicle transport along actin filament. Predicted to be part of myosin complex. Predicted to be active in several cellular components, including actin cytoskeleton; microvillus; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1H	NM_001101421.4	c.244A>T	p.Met82Leu	missense_variant	Exon 3 of 32	ENST00000310903.10	NP_001094891.4
MYO1H	XM_011538223.3	c.196A>T	p.Met66Leu	missense_variant	Exon 4 of 34		XP_011536525.1
MYO1H	XM_047428738.1	c.196A>T	p.Met66Leu	missense_variant	Exon 2 of 31		XP_047284694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1H	ENST00000310903.10	c.244A>T	p.Met82Leu	missense_variant	Exon 3 of 32	5	NM_001101421.4	ENSP00000439182.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436508 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 711918

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: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Benign	0.96
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.8	.;N
REVEL	Uncertain	0.49
Sift	Uncertain	0.016	.;D
Sift4G	Benign	0.089	T;T
Vest4		0.57
MutPred		0.51		.;Gain of catalytic residue at E67 (P = 0.0065);
MVP		0.79
MPC		0.42
ClinPred		0.92	D
GERP RS		5.0
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs556070676; hg19: chr12-109831205;