1-203171155-C-G

Variant names:

• chr1-203171155-C-G
• rs530822593
• NM_004997.3:c.839G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004997.3(MYBPH):​c.839G>C​(p.Gly280Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYBPH NM_004997.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.86
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3751137).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004997.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPH	NM_004997.3	MANE Select	c.839G>C	p.Gly280Ala	missense	Exon 6 of 11	NP_004988.2	Q13203

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPH	ENST00000255416.9	TSL:1 MANE Select	c.839G>C	p.Gly280Ala	missense	Exon 6 of 11	ENSP00000255416.4	Q13203
	MYBPH	ENST00000966288.1		c.914G>C	p.Gly305Ala	missense	Exon 6 of 10	ENSP00000636347.1
	MYBPH	ENST00000966289.1		c.914G>C	p.Gly305Ala	missense	Exon 6 of 11	ENSP00000636348.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460252 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726398

African (AFR) AF: 0.0000299 AC: 1 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111238

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.98	D
Vest4		0.45
MutPred		0.55		Loss of helix (P = 0.3949)
MVP		0.68
MPC		0.55
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.56
gMVP		0.60
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs530822593; hg19: chr1-203140283;