rs2058101

Positions:

• chr17-10451657-T-A
• chr17-10451657-T-C
• chr17-10451657-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017533.2(MYH4):​c.3739-205A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH4 NM_017533.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.13

Genes affected

MYH4 (HGNC:7574): (myosin heavy chain 4) Enables double-stranded RNA binding activity. Involved in muscle contraction. Located in myofibril. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272736 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH4	NM_017533.2	c.3739-205A>T		intron_variant		ENST00000255381.2	NP_060003.2
MYH4	XM_017024676.2	c.3739-205A>T		intron_variant			XP_016880165.1
MYHAS	NR_125367.1	n.167+45419T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH4	ENST00000255381.2	c.3739-205A>T		intron_variant		1	NM_017533.2	ENSP00000255381.2
ENSG00000272736	ENST00000399342.6	n.206+45380T>A		intron_variant		3
ENSG00000272736	ENST00000581304.1	n.143+45419T>A		intron_variant		3
MYHAS	ENST00000587182.2	n.155+45419T>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.085
DANN	Benign	0.12

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: rs2058101; hg19: chr17-10354974;