17-10400944-G-A

Variant names:

• chr17-10400944-G-A
• rs3744552
• NM_002472.3:c.3270C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002472.3(MYH8):​c.3270C>T​(p.Ile1090Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,612,782 control chromosomes in the GnomAD database, including 259,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26507 hom., cov: 33)
  • Exomes 𝑓: 0.56 (232866 hom.)
• Consequence: MYH8 NM_002472.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.295
• Publications: 16 publications found

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]

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 17-10400944-G-A is Benign according to our data. Variant chr17-10400944-G-A is described in ClinVar as Benign. ClinVar VariationId is 129674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.295 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002472.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	NM_002472.3	MANE Select	c.3270C>T	p.Ile1090Ile	synonymous	Exon 26 of 40	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.77-5204G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	ENST00000403437.2	TSL:5 MANE Select	c.3270C>T	p.Ile1090Ile	synonymous	Exon 26 of 40	ENSP00000384330.2	P13535
	MYHAS	ENST00000399342.6	TSL:3	n.77-5204G>A		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.53-5204G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87907 AN: 151986 Hom.: 26487 Cov.: 33

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.603

GnomAD2 exomes AF: 0.494 AC: 123748 AN: 250446 AF XY: 0.493

Gnomad AFR exome AF: 0.707

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.538

Gnomad EAS exome AF: 0.113

Gnomad FIN exome AF: 0.518

Gnomad NFE exome AF: 0.587

Gnomad OTH exome AF: 0.539

GnomAD4 exome AF: 0.555 AC: 810901 AN: 1460680 Hom.: 232866 Cov.: 47 AF XY: 0.550 AC XY: 399595 AN XY: 726656

African (AFR) AF: 0.708 AC: 23706 AN: 33462

American (AMR) AF: 0.410 AC: 18335 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 13997 AN: 26130

East Asian (EAS) AF: 0.150 AC: 5969 AN: 39698

South Asian (SAS) AF: 0.348 AC: 30015 AN: 86236

European-Finnish (FIN) AF: 0.528 AC: 27933 AN: 52952

Middle Eastern (MID) AF: 0.561 AC: 3234 AN: 5766

European-Non Finnish (NFE) AF: 0.589 AC: 654955 AN: 1111378

Other (OTH) AF: 0.543 AC: 32757 AN: 60356

GnomAD4 genome AF: 0.578 AC: 87977 AN: 152102 Hom.: 26507 Cov.: 33 AF XY: 0.565 AC XY: 41995 AN XY: 74336

African (AFR) AF: 0.699 AC: 29011 AN: 41532

American (AMR) AF: 0.506 AC: 7734 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1864 AN: 3468

East Asian (EAS) AF: 0.134 AC: 690 AN: 5160

South Asian (SAS) AF: 0.332 AC: 1602 AN: 4822

European-Finnish (FIN) AF: 0.515 AC: 5441 AN: 10568

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.585 AC: 39738 AN: 67952

Other (OTH) AF: 0.602 AC: 1270 AN: 2110

Alfa AF: 0.584 Hom.: 74283

Bravo AF: 0.587

Asia WGS AF: 0.276 AC: 963 AN: 3478

EpiCase AF: 0.597

EpiControl AF: 0.592

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Hecht syndrome (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.3
DANN	Benign	0.73
PhyloP100		-0.29
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3744552; hg19: chr17-10304261; COSMIC: COSV67960036;