Variant 7-114942305-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001166345.3(MDFIC):c.125A>G(p.Asp42Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,571,122 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0000092 ( 1 hom. )

Consequence

MDFIC
NM_001166345.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044249475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDFIC	NM_001166345.3 linkuse as main transcript	c.125A>G	p.Asp42Gly	missense_variant	3/5	ENST00000393486.6	NP_001159817.1	Q9P1T7-2
MDFIC	NM_199072.5 linkuse as main transcript	c.452A>G	p.Asp151Gly	missense_variant	3/5		NP_951038.1	Q9P1T7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MDFIC	ENST00000393486.6 linkuse as main transcript	c.125A>G	p.Asp42Gly	missense_variant	3/5	1	NM_001166345.3	ENSP00000377126.1	Q9P1T7-2
MDFIC	ENST00000427207.5 linkuse as main transcript	c.83A>G	p.Asp28Gly	missense_variant	2/4	3		ENSP00000392098.1	H7BZY3
MDFIC	ENST00000498196 linkuse as main transcript	c.-41A>G		5_prime_UTR_variant	2/4	4		ENSP00000418337.1	C9J784
MDFIC	ENST00000431629.5 linkuse as main transcript	n.95A>G		non_coding_transcript_exon_variant	2/5	5		ENSP00000416668.1	H7C4B9

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000916

AC:

AN:

1418892

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

707546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.28e-7

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Jul 20, 2021

The c.452A>G (p.D151G) alteration is located in exon 3 (coding exon 3) of the MDFIC gene. This alteration results from a A to G substitution at nucleotide position 452, causing the aspartic acid (D) at amino acid position 151 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

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

.;T;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.69

T;T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.044

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.7

N;N;.;D

REVEL

Benign

0.050

Sift

Benign

0.047

D;D;.;D

Sift4G

Benign

0.16

T;D;T;D

Polyphen

0.63

.;P;.;.

Vest4

0.30

MutPred

0.12

.;Gain of methylation at K41 (P = 0.0786);.;.;

MVP

0.24

ClinPred

0.27

GERP RS

1.7

Varity_R

0.059

gMVP

0.14

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