chr1-109295161-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001010985.3(MYBPHL):c.1004C>T(p.Ala335Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
MYBPHL
NM_001010985.3 missense
NM_001010985.3 missense
Scores
11
6
2
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
MYBPHL (HGNC:30434): (myosin binding protein H like) This gene encodes a protein with two immunoglobulin superfamily domains and a fibronectin 3 domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.764
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYBPHL | NM_001010985.3 | c.1004C>T | p.Ala335Val | missense_variant | 7/9 | ENST00000357155.2 | NP_001010985.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYBPHL | ENST00000357155.2 | c.1004C>T | p.Ala335Val | missense_variant | 7/9 | 1 | NM_001010985.3 | ENSP00000349678 | P1 | |
MYBPHL | ENST00000477962.1 | n.286C>T | non_coding_transcript_exon_variant | 2/4 | 1 | |||||
MYBPHL | ENST00000489706.5 | n.257C>T | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152146Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251392Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135862
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461760Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727184
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GnomAD4 genome AF: 0.0000919 AC: 14AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74446
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2021 | The c.1004C>T (p.A335V) alteration is located in exon 7 (coding exon 7) of the MYBPHL gene. This alteration results from a C to T substitution at nucleotide position 1004, causing the alanine (A) at amino acid position 335 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at