rs149778217

Variant names:

• chr1-203170324-C-A
• rs149778217
• NM_004997.3:c.1060G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-203170324-C-A
• chr1-203170324-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004997.3(MYBPH):​c.1060G>T​(p.Val354Phe) 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. 13/21 in silico tools predict a benign outcome for this variant. 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. V354I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYBPH NM_004997.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16543418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPH	NM_004997.3	c.1060G>T	p.Val354Phe	missense_variant	Exon 7 of 11	ENST00000255416.9	NP_004988.2
MYBPH	XM_047421205.1	c.1183G>T	p.Val395Phe	missense_variant	Exon 8 of 12		XP_047277161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPH	ENST00000255416.9	c.1060G>T	p.Val354Phe	missense_variant	Exon 7 of 11	1	NM_004997.3	ENSP00000255416.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.78	T;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.8	.;D
REVEL	Benign	0.19
Sift	Benign	0.036	.;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.78	.;P
Vest4		0.27
MutPred		0.18		Loss of ubiquitination at K356 (P = 0.0747);Loss of ubiquitination at K356 (P = 0.0747);
MVP		0.25
MPC		0.19
ClinPred		0.88	D
GERP RS		-5.7
Varity_R		0.15
gMVP		0.60

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: rs149778217; hg19: chr1-203139452;