rs3744551

Variant names:

• chr17-10390378-C-G
• rs3744551
• NM_002472.3:c.*76G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-10390378-C-G
• chr17-10390378-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002472.3(MYH8):​c.*76G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 1,555,640 control chromosomes in the GnomAD database, including 1,601 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (79 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1522 hom.)
• Consequence: MYH8 NM_002472.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.614
• Publications: 4 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=-0.65).
• BP6: Variant 17-10390378-C-G is Benign according to our data. Variant chr17-10390378-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 321619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0513 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.*76G>C		3_prime_UTR	Exon 40 of 40	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.76+7171C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	ENST00000403437.2	TSL:5 MANE Select	c.*76G>C		3_prime_UTR	Exon 40 of 40	ENSP00000384330.2	P13535
	MYHAS	ENST00000399342.6	TSL:3	n.76+7171C>G		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.52+7171C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4435 AN: 152146 Hom.: 79 Cov.: 33

Gnomad AFR AF: 0.00842

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.0187

GnomAD4 exome AF: 0.0427 AC: 59959 AN: 1403376 Hom.: 1522 Cov.: 24 AF XY: 0.0432 AC XY: 30305 AN XY: 701620

African (AFR) AF: 0.00617 AC: 198 AN: 32100

American (AMR) AF: 0.0120 AC: 534 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.0152 AC: 392 AN: 25780

East Asian (EAS) AF: 0.00969 AC: 381 AN: 39334

South Asian (SAS) AF: 0.0526 AC: 4462 AN: 84892

European-Finnish (FIN) AF: 0.0366 AC: 1946 AN: 53148

Middle Eastern (MID) AF: 0.0343 AC: 138 AN: 4024

European-Non Finnish (NFE) AF: 0.0469 AC: 49809 AN: 1061148

Other (OTH) AF: 0.0360 AC: 2099 AN: 58350

GnomAD4 genome AF: 0.0291 AC: 4436 AN: 152264 Hom.: 79 Cov.: 33 AF XY: 0.0290 AC XY: 2157 AN XY: 74444

African (AFR) AF: 0.00840 AC: 349 AN: 41550

American (AMR) AF: 0.0191 AC: 292 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5188

South Asian (SAS) AF: 0.0510 AC: 246 AN: 4828

European-Finnish (FIN) AF: 0.0405 AC: 430 AN: 10606

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0434 AC: 2954 AN: 68008

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.0329 Hom.: 8

Bravo AF: 0.0253

Asia WGS AF: 0.0440 AC: 152 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hecht syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.7
DANN	Benign	0.71
PhyloP100		0.61
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: rs3744551; hg19: chr17-10293695;