rs9899024

Variant names:

• chr17-10401255-G-T
• rs9899024
• NM_002472.3:c.3108+20C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002472.3(MYH8):​c.3108+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000973 in 1,614,000 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (9 hom.)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.18
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-10401255-G-T is Benign according to our data. Variant chr17-10401255-G-T is described in ClinVar as Benign. ClinVar VariationId is 258719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00523 (796/152236) while in subpopulation AFR AF = 0.0184 (766/41548). AF 95% confidence interval is 0.0174. There are 7 homozygotes in GnomAd4. There are 365 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 796 AD gene.

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.3108+20C>A		intron	N/A	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.77-4893G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	ENST00000403437.2	TSL:5 MANE Select	c.3108+20C>A		intron	N/A	ENSP00000384330.2	P13535
	MYHAS	ENST00000399342.6	TSL:3	n.77-4893G>T		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.53-4893G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00520 AC: 791 AN: 152118 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00142 AC: 356 AN: 251448 AF XY: 0.00104

Gnomad AFR exome AF: 0.0203

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000530 AC: 775 AN: 1461764 Hom.: 9 Cov.: 34 AF XY: 0.000479 AC XY: 348 AN XY: 727184

African (AFR) AF: 0.0192 AC: 642 AN: 33474

American (AMR) AF: 0.000805 AC: 36 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111934

Other (OTH) AF: 0.00128 AC: 77 AN: 60388

GnomAD4 genome AF: 0.00523 AC: 796 AN: 152236 Hom.: 7 Cov.: 32 AF XY: 0.00490 AC XY: 365 AN XY: 74416

African (AFR) AF: 0.0184 AC: 766 AN: 41548

American (AMR) AF: 0.00124 AC: 19 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00248 Hom.: 0

Bravo AF: 0.00629

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.13
DANN	Benign	0.40
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs9899024; hg19: chr17-10304572;