7-114922546-G-T

Variant names:

Variant summary

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

The NM_001166345.3(MDFIC):c.-198G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,266,490 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00091 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

MDFIC
NM_001166345.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.410

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0046138167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDFIC	NM_001166345.3 link	c.-198G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	ENST00000393486.6	NP_001159817.1	Q9P1T7-2
MDFIC	NM_001166345.3 link	c.-198G>T		5_prime_UTR_variant	Exon 1 of 5	ENST00000393486.6	NP_001159817.1	Q9P1T7-2
MDFIC	NM_199072.5 link	c.130G>T	p.Gly44Cys	missense_variant	Exon 1 of 5		NP_951038.1	Q9P1T7-1
MDFIC	NM_001166346.1 link	c.130G>T	p.Gly44Cys	missense_variant	Exon 1 of 3		NP_001159818.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MDFIC	ENST00000393486 link	c.-198G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	1	NM_001166345.3	ENSP00000377126.1	Q9P1T7-2
MDFIC	ENST00000393486 link	c.-198G>T	5_prime_UTR_variant	Exon 1 of 5	1	NM_001166345.3	ENSP00000377126.1	Q9P1T7-2
MDFIC	ENST00000448022.1 link	c.-198G>T	upstream_gene_variant		2		ENSP00000412153.1	C9J104

Frequencies

GnomAD3 genomes

AF:

0.000880

AC:

134

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00299

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000110

AC:

AN:

27330

Hom.:

AF XY:

0.000144

AC XY:

AN XY:

13884

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000898

AC:

100

AN:

1114182

Hom.:

Cov.:

AF XY:

0.0000851

AC XY:

AN XY:

528784

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.000216

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000118

Gnomad4 OTH exome

AF:

0.000247

GnomAD4 genome

AF:

0.000913

AC:

139

AN:

152308

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00310

Gnomad4 AMR

AF:

0.000326

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000641

Hom.:

Bravo

AF:

0.000948

ESP6500AA

AF:

0.000903

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000147

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.130G>T (p.G44C) alteration is located in exon 1 (coding exon 1) of the MDFIC gene. This alteration results from a G to T substitution at nucleotide position 130, causing the glycine (G) at amino acid position 44 to be replaced by a cysteine (C). 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

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.3

DANN

Benign

0.96

Eigen

Benign

-0.87

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.31

T;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.99

PROVEAN

Benign

0.040

N;.

REVEL

Benign

0.0070

Sift

Uncertain

0.014

D;.

Sift4G

Uncertain

0.016

D;D

Vest4

0.15

MVP

0.076

ClinPred

0.043

GERP RS

-2.3

gMVP

0.13

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