12-69936587-CAA-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182530.3(MYRFL):c.2181_2182del(p.Arg728ThrfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYRFL NM_182530.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.258

Genes affected

MYRFL (HGNC:26316): (myelin regulatory factor like) Predicted to enable DNA-binding transcription factor activity and sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated and protein autoprocessing. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PRANCR (HGNC:51126): (progenitor renewal associated non-coding RNA)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRFL	NM_182530.3	c.2181_2182del	p.Arg728ThrfsTer3	frameshift_variant	19/25	ENST00000552032.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRFL	ENST00000552032.7	c.2181_2182del	p.Arg728ThrfsTer3	frameshift_variant	19/25	5	NM_182530.3	P2
PRANCR	ENST00000549419.6	n.153-32170_153-32169del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2018

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Computational scores

Source: dbNSFP v4.3

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: rs1555258490; hg19: chr12-70330367;