rs2058099

chr17-10459429-A-Cchr17-10459429-A-Gchr17-10459429-A-T

Variant summary

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

The NM_017533.2(MYH4):c.1417-8T>G variant causes a splice region, splice polypyrimidine tract, 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYH4 NM_017533.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.004743
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

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]

(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=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH4	NM_017533.2	c.1417-8T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000255381.2
MYHAS	NR_125367.1	n.167+53191A>C		intron_variant, non_coding_transcript_variant
MYH4	XM_017024676.2	c.1417-8T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH4	ENST00000255381.2	c.1417-8T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_017533.2	P1
	ENST00000399342.6	n.206+53152A>C		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1	n.143+53191A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.0
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0047
dbscSNV1_RF	Benign	0.19
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: rs2058099; hg19: chr17-10362746;