NM_002472.3:c.1417-111C>T

Variant names:

• chr17-10411058-G-A
• rs12601552
• NM_002472.3:c.1417-111C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002472.3(MYH8):​c.1417-111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,553,184 control chromosomes in the GnomAD database, including 128,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12118 hom., cov: 32)
  • Exomes 𝑓: 0.39 (116370 hom.)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.26

Genes affected

MYH8 (HGNC:7578): (myosin heavy chain 8) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]

ENSG00000272736 (HGNC:):

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 17-10411058-G-A is Benign according to our data. Variant chr17-10411058-G-A is described in ClinVar as [Benign]. Clinvar id is 1181307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH8	NM_002472.3	c.1417-111C>T		intron_variant	Intron 14 of 39	ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1	n.167+4820G>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2	c.1417-111C>T		intron_variant	Intron 14 of 39	5	NM_002472.3	ENSP00000384330.2
ENSG00000272736	ENST00000399342.6	n.206+4781G>A		intron_variant	Intron 2 of 3	3
ENSG00000272736	ENST00000581304.1	n.143+4820G>A		intron_variant	Intron 2 of 3	3
MYHAS	ENST00000587182.2	n.155+4820G>A		intron_variant	Intron 2 of 10	5

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57577 AN: 151830 Hom.: 12109 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.392 AC: 549394 AN: 1401236 Hom.: 116370 AF XY: 0.398 AC XY: 277141 AN XY: 696248

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.847

Gnomad4 SAS exome AF: 0.612

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.379 AC: 57623 AN: 151948 Hom.: 12118 Cov.: 32 AF XY: 0.393 AC XY: 29184 AN XY: 74246

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.369

Alfa AF: 0.357 Hom.: 1221

Bravo AF: 0.373

Asia WGS AF: 0.712 AC: 2472 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.21
DANN	Benign	0.48

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: rs12601552; hg19: chr17-10314375;