NM_002472.3:c.1148-230G>A

Variant names:

• chr17-10412958-C-T
• rs2041125
• NM_002472.3:c.1148-230G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002472.3(MYH8):​c.1148-230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,058 control chromosomes in the GnomAD database, including 12,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (12098 hom., cov: 32)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.483
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-10412958-C-T is Benign according to our data. Variant chr17-10412958-C-T is described in ClinVar as Benign. ClinVar VariationId is 1277987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 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.1148-230G>A		intron	N/A	NP_002463.2
	MYHAS	NR_125367.1		n.167+6720C>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.1148-230G>A		intron	N/A	ENSP00000384330.2
	MYHAS	ENST00000399342.6	TSL:3	n.206+6681C>T		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.143+6720C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57515 AN: 151940 Hom.: 12089 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.367

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.379 AC: 57561 AN: 152058 Hom.: 12098 Cov.: 32 AF XY: 0.393 AC XY: 29183 AN XY: 74324

African (AFR) AF: 0.274 AC: 11366 AN: 41466

American (AMR) AF: 0.459 AC: 7008 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1375 AN: 3468

East Asian (EAS) AF: 0.866 AC: 4480 AN: 5172

South Asian (SAS) AF: 0.633 AC: 3048 AN: 4814

European-Finnish (FIN) AF: 0.436 AC: 4615 AN: 10578

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24398 AN: 67974

Other (OTH) AF: 0.369 AC: 780 AN: 2112

Alfa AF: 0.233 Hom.: 521

Bravo AF: 0.372

Asia WGS AF: 0.711 AC: 2461 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs2041125; hg19: chr17-10316275; COSMIC: COSV67961938;