chr1-109296296-C-G

Variant names:

• chr1-109296296-C-G
• rs629001
• NM_001010985.3:c.805G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001010985.3(MYBPHL):​c.805G>C​(p.Asp269His) 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 pathogenic 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. D269N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MYBPHL NM_001010985.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96

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]

ACMG classification

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, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPHL	NM_001010985.3	c.805G>C	p.Asp269His	missense_variant	Exon 6 of 9	ENST00000357155.2	NP_001010985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPHL	ENST00000357155.2	c.805G>C	p.Asp269His	missense_variant	Exon 6 of 9	1	NM_001010985.3	ENSP00000349678.1
MYBPHL	ENST00000477962.1	n.150-999G>C		intron_variant	Intron 1 of 3	1
MYBPHL	ENST00000489706.5	n.58G>C		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.59	P
Vest4		0.53
MutPred		0.64		Gain of catalytic residue at D269 (P = 0.0084);
MVP		0.87
MPC		0.68
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.43
gMVP		0.40

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: rs629001; hg19: chr1-109838918;