12-101614323-T-TGA

Position:

• chr12-101614323-T-TGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002465.4(MYBPC1):​c.26-172_26-171insAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 151,592 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0033 (2 hom., cov: 31)
• Consequence: MYBPC1 NM_002465.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.796

Genes affected

MYBPC1 (HGNC:7549): (myosin binding protein C1) This gene encodes a member of the myosin-binding protein C family. Myosin-binding protein C family members are myosin-associated proteins found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The encoded protein is the slow skeletal muscle isoform of myosin-binding protein C and plays an important role in muscle contraction by recruiting muscle-type creatine kinase to myosin filaments. Mutations in this gene are associated with distal arthrogryposis type I. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

LOC105369938 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-101614323-T-TGA is Benign according to our data. Variant chr12-101614323-T-TGA is described in ClinVar as [Likely_benign]. Clinvar id is 1311046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00334 (506/151592) while in subpopulation AFR AF= 0.0101 (417/41232). AF 95% confidence interval is 0.00931. There are 2 homozygotes in gnomad4. There are 245 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC1	NM_002465.4	c.26-172_26-171insAG		intron_variant		ENST00000361466.7	NP_002456.2
LOC105369938	XR_001749279.2	n.722+230_722+231insTC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC1	ENST00000361466.7	c.26-172_26-171insAG		intron_variant		1	NM_002465.4	ENSP00000354849	A2

Frequencies

GnomAD3 genomes AF: 0.00333 AC: 504 AN: 151480 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000973

Gnomad SAS AF: 0.00397

Gnomad FIN AF: 0.0000947

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000486

Gnomad OTH AF: 0.00289

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00334 AC: 506 AN: 151592 Hom.: 2 Cov.: 31 AF XY: 0.00331 AC XY: 245 AN XY: 74042

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.00158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000975

Gnomad4 SAS AF: 0.00418

Gnomad4 FIN AF: 0.0000947

Gnomad4 NFE AF: 0.000486

Gnomad4 OTH AF: 0.00286

Alfa AF: 0.0000627 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1288757474; hg19: chr12-102008101;