17-10443388-A-C

Position:

• chr17-10443388-A-C

Variant summary

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

The NM_017533.2(MYH4):​c.5807T>G​(p.Ile1936Arg) variant causes a missense 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH4 NM_017533.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24

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 (MetaRNN=0.06188056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH4	NM_017533.2	c.5807T>G	p.Ile1936Arg	missense_variant	40/40	ENST00000255381.2
MYHAS	NR_125367.1	n.167+37150A>C		intron_variant, non_coding_transcript_variant
MYH4	XM_017024676.2	c.5807T>G	p.Ile1936Arg	missense_variant	38/38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH4	ENST00000255381.2	c.5807T>G	p.Ile1936Arg	missense_variant	40/40	1	NM_017533.2	P1
	ENST00000399342.6	n.206+37111A>C		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1	n.143+37150A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.5807T>G (p.I1936R) alteration is located in exon 40 (coding exon 38) of the MYH4 gene. This alteration results from a T to G substitution at nucleotide position 5807, causing the isoleucine (I) at amino acid position 1936 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.0082	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-0.52	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.27
Sift	Benign	0.22	T
Sift4G	Benign	0.56	T
Polyphen		0.0050	B
Vest4		0.22
MutPred		0.16		Gain of MoRF binding (P = 0.0065);
MVP		0.37
MPC		0.30
ClinPred		0.072	T
GERP RS		2.9
Varity_R		0.17
gMVP		0.056

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-10346705;