1-203170342-G-A

Position:

• chr1-203170342-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004997.3(MYBPH):​c.1042C>T​(p.Leu348Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L348P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYBPH NM_004997.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28

Genes affected

MYBPH (HGNC:7552): (myosin binding protein H) Predicted to be a structural constituent of muscle. Predicted to be involved in regulation of striated muscle contraction. Predicted to be located in myosin filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPH	NM_004997.3	c.1042C>T	p.Leu348Phe	missense_variant	7/11	ENST00000255416.9	NP_004988.2
MYBPH	XM_047421205.1	c.1165C>T	p.Leu389Phe	missense_variant	8/12		XP_047277161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPH	ENST00000255416.9	c.1042C>T	p.Leu348Phe	missense_variant	7/11	1	NM_004997.3	ENSP00000255416.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 13, 2024

The c.1042C>T (p.L348F) alteration is located in exon 7 (coding exon 7) of the MYBPH gene. This alteration results from a C to T substitution at nucleotide position 1042, causing the leucine (L) at amino acid position 348 to be replaced by a phenylalanine (F). 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	0.28
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.4	.;D
REVEL	Benign	0.12
Sift	Benign	0.062	.;T
Sift4G	Benign	0.084	T;T
Polyphen		0.62	.;P
Vest4		0.51
MutPred		0.37		Loss of stability (P = 0.1897);Loss of stability (P = 0.1897);
MVP		0.66
MPC		0.24
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.28
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-203139470;