NM_004533.4:c.120C>T

Variant names:

• chr19-50435786-C-T
• rs1355213778
• NM_004533.4:c.120C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004533.4(MYBPC2):​c.120C>T​(p.Pro40Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000096 in 1,457,680 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: MYBPC2 NM_004533.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.961
• Publications: 0 publications found

Genes affected

MYBPC2 (HGNC:7550): (myosin binding protein C2) This gene encodes a member of the myosin-binding protein C family. This family includes the fast-, slow- and cardiac-type isoforms, each of which is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The protein encoded by this locus is referred to as the fast-type isoform. Mutations in the related but distinct genes encoding the slow-type and cardiac-type isoforms have been associated with distal arthrogryposis, type 1 and hypertrophic cardiomyopathy, respectively. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 19-50435786-C-T is Benign according to our data. Variant chr19-50435786-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.961 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004533.4. 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
	MYBPC2	NM_004533.4	MANE Select	c.120C>T	p.Pro40Pro	synonymous	Exon 3 of 28	NP_004524.3	A0A140VJQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC2	ENST00000357701.6	TSL:1 MANE Select	c.120C>T	p.Pro40Pro	synonymous	Exon 3 of 28	ENSP00000350332.4	Q14324
	MYBPC2	ENST00000966357.1		c.120C>T	p.Pro40Pro	synonymous	Exon 3 of 28	ENSP00000636416.1
	MYBPC2	ENST00000966353.1		c.249C>T	p.Pro83Pro	synonymous	Exon 4 of 29	ENSP00000636412.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244410 AF XY: 0.00000752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000905

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000960 AC: 14 AN: 1457680 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 724400

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39560

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000991 AC: 11 AN: 1109450

Other (OTH) AF: 0.0000166 AC: 1 AN: 60098

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.77
DANN	Benign	0.61
PhyloP100		-0.96

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: rs1355213778; hg19: chr19-50939043;