Variant 12-69880291-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_182530.3(MYRFL):c.555G>A(p.Pro185=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 702,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 0 hom. )

Consequence

MYRFL
NM_182530.3 splice_region, synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.425

Variant links:

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]

MYRFL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 12-69880291-G-A is Benign according to our data. Variant chr12-69880291-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643172.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.425 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRFL	NM_182530.3 linkuse as main transcript	c.555G>A	p.Pro185=	splice_region_variant, synonymous_variant	5/25	ENST00000552032.7	NP_872336.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRFL	ENST00000552032.7 linkuse as main transcript	c.555G>A	p.Pro185=	splice_region_variant, synonymous_variant	5/25	5	NM_182530.3	ENSP00000448753	P2
MYRFL	ENST00000547771.6 linkuse as main transcript	c.555G>A	p.Pro185=	splice_region_variant, synonymous_variant	5/25	5		ENSP00000449598	A2

Frequencies

GnomAD3 genomes

AF:

0.00196

AC:

299

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00688

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00287

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00141

AC:

189

AN:

133624

Hom.:

AF XY:

0.00132

AC XY:

AN XY:

72730

show subpopulations

Gnomad AFR exome

AF:

0.000466

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.000121

Gnomad EAS exome

AF:

0.0000954

Gnomad SAS exome

AF:

0.0000447

Gnomad FIN exome

AF:

0.00744

Gnomad NFE exome

AF:

0.00248

Gnomad OTH exome

AF:

0.00146

GnomAD4 exome

AF:

0.00194

AC:

1070

AN:

550198

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

524

AN XY:

297860

show subpopulations

Gnomad4 AFR exome

AF:

0.000506

Gnomad4 AMR exome

AF:

0.000260

Gnomad4 ASJ exome

AF:

0.0000499

Gnomad4 EAS exome

AF:

0.000374

Gnomad4 SAS exome

AF:

0.000112

Gnomad4 FIN exome

AF:

0.00494

Gnomad4 NFE exome

AF:

0.00259

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00196

AC:

299

AN:

152336

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00688

Gnomad4 NFE

AF:

0.00287

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00158

Hom.:

Bravo

AF:

0.00153

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

MYRFL: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over