12-109404049-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001101421.4(MYO1H):c.818C>G(p.Ser273Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 1,613,562 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (183 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (169 hom.)
• Consequence: MYO1H NM_001101421.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.90

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031850636).
• BP6: Variant 12-109404049-C-G is Benign according to our data. Variant chr12-109404049-C-G is described in ClinVar as [Benign]. Clinvar id is 768581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1H	NM_001101421.4	c.818C>G	p.Ser273Cys	missense_variant	7/32	ENST00000310903.10
MYO1H	XM_011538223.3	c.770C>G	p.Ser257Cys	missense_variant	8/34
MYO1H	XM_047428738.1	c.770C>G	p.Ser257Cys	missense_variant	6/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1H	ENST00000310903.10	c.818C>G	p.Ser273Cys	missense_variant	7/32	5	NM_001101421.4	P1
MYO1H	ENST00000542883.1	n.148C>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4203 AN: 152090 Hom.: 181 Cov.: 33

Gnomad AFR AF: 0.0953

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0211

GnomAD3 exomes AF: 0.00717 AC: 1783 AN: 248518 Hom.: 67 AF XY: 0.00531 AC XY: 716 AN XY: 134836

Gnomad AFR exome AF: 0.0984

Gnomad AMR exome AF: 0.00532

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000461

Gnomad OTH exome AF: 0.00398

GnomAD4 exome AF: 0.00304 AC: 4439 AN: 1461356 Hom.: 169 Cov.: 30 AF XY: 0.00262 AC XY: 1904 AN XY: 726944

Gnomad4 AFR exome AF: 0.0977

Gnomad4 AMR exome AF: 0.00580

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000348

Gnomad4 OTH exome AF: 0.00754

GnomAD4 genome AF: 0.0277 AC: 4215 AN: 152206 Hom.: 183 Cov.: 33 AF XY: 0.0259 AC XY: 1929 AN XY: 74426

Gnomad4 AFR AF: 0.0954

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.00843 Hom.: 10

Bravo AF: 0.0312

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0949 AC: 359

ESP6500EA AF: 0.000486 AC: 4

ExAC AF: 0.00913 AC: 1103

Asia WGS AF: 0.00635 AC: 23 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000535

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.37	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	23
Dann	Uncertain	0.99
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.65	T;T
MetaRNN	Benign	0.0032	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.37	T
REVEL	Uncertain	0.47
Sift4G	Uncertain	0.015	D;D
Vest4		0.40
MVP		0.69
MPC		0.37
ClinPred		0.047	T
GERP RS		4.8
gMVP		0.27

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: rs61740371; hg19: chr12-109841854;