12-109401121-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001101421.4(MYO1H):c.599G>T(p.Ser200Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00354 in 1,613,944 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (17 hom.)
• Consequence: MYO1H NM_001101421.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.49

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017060041).
• BP6: Variant 12-109401121-G-T is Benign according to our data. Variant chr12-109401121-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 717107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1H	NM_001101421.4	c.599G>T	p.Ser200Ile	missense_variant	6/32	ENST00000310903.10
MYO1H	XM_011538223.3	c.551G>T	p.Ser184Ile	missense_variant	7/34
MYO1H	XM_047428738.1	c.551G>T	p.Ser184Ile	missense_variant	5/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1H	ENST00000310903.10	c.599G>T	p.Ser200Ile	missense_variant	6/32	5	NM_001101421.4	P1

Frequencies

GnomAD3 genomes AF: 0.00207 AC: 315 AN: 152178 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00337

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00216 AC: 537 AN: 249032 Hom.: 3 AF XY: 0.00216 AC XY: 292 AN XY: 135082

Gnomad AFR exome AF: 0.000711

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00666

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.000557

Gnomad NFE exome AF: 0.00309

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00369 AC: 5398 AN: 1461648 Hom.: 17 Cov.: 30 AF XY: 0.00353 AC XY: 2570 AN XY: 727106

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.00777

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00102

Gnomad4 FIN exome AF: 0.000824

Gnomad4 NFE exome AF: 0.00431

Gnomad4 OTH exome AF: 0.00308

GnomAD4 genome AF: 0.00207 AC: 315 AN: 152296 Hom.: 1 Cov.: 32 AF XY: 0.00187 AC XY: 139 AN XY: 74472

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00337

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00331 Hom.: 0

Bravo AF: 0.00212

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00804 AC: 31

ESP6500AA AF: 0.000503 AC: 2

ESP6500EA AF: 0.00360 AC: 30

ExAC AF: 0.00211 AC: 255

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00278

EpiControl AF: 0.00308

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	MYO1H: BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	25
Dann	Uncertain	1.0
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.017	T;T
MetaSVM	Uncertain	0.50	D
MutationTaster	Benign	0.94	D;D
PrimateAI	Uncertain	0.57	T
REVEL	Pathogenic	0.69
Sift4G	Pathogenic	0.0010	D;D
Vest4		0.63
MVP		0.86
MPC		0.43
ClinPred		0.042	T
GERP RS		4.5
gMVP		0.49

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

LitVar

Other links and lift over

dbSNP: rs200532551; hg19: chr12-109838926; COSMIC: COSV60443438; COSMIC: COSV60443438;