Variant 7-114922989-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_199072.5(MDFIC):c.283C>G(p.Arg95Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000076 in 1,527,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

MDFIC
NM_199072.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0740

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013249993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDFIC	NM_001166345.3 linkuse as main transcript	c.-45C>G		5_prime_UTR_variant	2/5	ENST00000393486.6	NP_001159817.1	Q9P1T7-2
MDFIC	NM_199072.5 linkuse as main transcript	c.283C>G	p.Arg95Gly	missense_variant	2/5		NP_951038.1	Q9P1T7-1
MDFIC	NM_001166346.1 linkuse as main transcript	c.283C>G	p.Arg95Gly	missense_variant	2/3		NP_001159818.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MDFIC	ENST00000393486 linkuse as main transcript	c.-45C>G	5_prime_UTR_variant	2/5	1	NM_001166345.3	ENSP00000377126.1	Q9P1T7-2
MDFIC	ENST00000423503.1 linkuse as main transcript	c.-45C>G	5_prime_UTR_variant	1/2	1		ENSP00000401623.1	C9J104
MDFIC	ENST00000448022.1 linkuse as main transcript	c.-45C>G	5_prime_UTR_variant	2/3	2		ENSP00000412153.1	C9J104

Frequencies

GnomAD3 genomes

AF:

0.0000530

AC:

AN:

150880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000171

AC:

AN:

164092

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

92754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00160

Gnomad SAS exome

AF:

0.000477

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000425

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000785

AC:

108

AN:

1376302

Hom.:

Cov.:

AF XY:

0.0000936

AC XY:

AN XY:

683608

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000606

Gnomad4 SAS exome

AF:

0.000758

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000177

Gnomad4 OTH exome

AF:

0.000144

GnomAD4 genome

AF:

0.0000530

AC:

AN:

150990

Hom.:

Cov.:

AF XY:

0.0000813

AC XY:

AN XY:

73776

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000937

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000166

AC:

Asia WGS

AF:

0.00116

AC:

AN:

3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.283C>G (p.R95G) alteration is located in exon 2 (coding exon 2) of the MDFIC gene. This alteration results from a C to G substitution at nucleotide position 283, causing the arginine (R) at amino acid position 95 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.80

PROVEAN

Benign

-0.20

N;.

REVEL

Benign

0.051

Sift

Uncertain

0.016

D;.

Sift4G

Benign

0.11

T;T

Vest4

0.27

MutPred

0.20

Gain of loop (P = 0.0051);Gain of loop (P = 0.0051);

MVP

0.22

ClinPred

0.095

GERP RS

1.6

gMVP

0.095

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