Variant 7-114922583-AGAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_199072.5(MDFIC):c.185_187delGGA(p.Arg62del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,249,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

MDFIC
NM_199072.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.927

Variant links:

Genes affected

MDFIC (HGNC:28870): (MyoD family inhibitor domain containing) This gene product is a member of a family of proteins characterized by a specific cysteine-rich C-terminal domain, which is involved in transcriptional regulation of viral genome expression. Alternative translation initiation from an upstream non-AUG (GUG), and an in-frame, downstream AUG codon, results in the production of two isoforms, p40 and p32, respectively, which have different subcellular localization; p32 is mainly found in the cytoplasm, whereas p40 is targeted to the nucleolus. Both isoforms have transcriptional regulatory activity that is attributable to the cysteine-rich C-terminal domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

MDFIC links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 7-114922583-AGAG-A is Benign according to our data. Variant chr7-114922583-AGAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 3346872.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDFIC	NM_001166345.3 linkuse as main transcript	c.-143_-141delGGA		5_prime_UTR_variant	1/5	ENST00000393486.6	NP_001159817.1	Q9P1T7-2
MDFIC	NM_199072.5 linkuse as main transcript	c.185_187delGGA	p.Arg62del	disruptive_inframe_deletion	1/5		NP_951038.1	Q9P1T7-1
MDFIC	NM_001166346.1 linkuse as main transcript	c.185_187delGGA	p.Arg62del	disruptive_inframe_deletion	1/3		NP_001159818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDFIC	ENST00000393486 linkuse as main transcript	c.-143_-141delGGA		5_prime_UTR_variant	1/5	1	NM_001166345.3	ENSP00000377126.1		Q9P1T7-2
MDFIC	ENST00000448022.1 linkuse as main transcript	c.-143_-141delGGA		5_prime_UTR_variant	1/3	2		ENSP00000412153.1		C9J104

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00341

AC:

AN:

25240

Hom.:

AF XY:

0.00410

AC XY:

AN XY:

12440

show subpopulations

Gnomad AFR exome

AF:

0.00196

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00340

Gnomad EAS exome

AF:

0.00253

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00576

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000298

AC:

327

AN:

1098176

Hom.:

AF XY:

0.000411

AC XY:

214

AN XY:

520970

show subpopulations

Gnomad4 AFR exome

AF:

0.000259

Gnomad4 AMR exome

AF:

0.000227

Gnomad4 ASJ exome

AF:

0.000423

Gnomad4 EAS exome

AF:

0.000635

Gnomad4 SAS exome

AF:

0.00315

Gnomad4 FIN exome

AF:

0.000954

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.000297

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151688

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MDFIC-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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