Variant 7-114922594-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_199072.5(MDFIC):c.178A>T(p.Arg60Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,267,208 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

MDFIC
NM_199072.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16224694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDFIC	NM_001166345.3 linkuse as main transcript	c.-150A>T		5_prime_UTR_variant	1/5	ENST00000393486.6	NP_001159817.1	Q9P1T7-2
MDFIC	NM_199072.5 linkuse as main transcript	c.178A>T	p.Arg60Trp	missense_variant	1/5		NP_951038.1	Q9P1T7-1
MDFIC	NM_001166346.1 linkuse as main transcript	c.178A>T	p.Arg60Trp	missense_variant	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.-150A>T		5_prime_UTR_variant	1/5	1	NM_001166345.3	ENSP00000377126.1		Q9P1T7-2
MDFIC	ENST00000448022.1 linkuse as main transcript	c.-150A>T		5_prime_UTR_variant	1/3	2		ENSP00000412153.1		C9J104

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

AF:

0.0000377

AC:

AN:

1115488

Hom.:

Cov.:

AF XY:

0.0000264

AC XY:

AN XY:

529442

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000440

Gnomad4 OTH exome

AF:

0.0000224

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151720

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74070

show subpopulations

Gnomad4 AFR

AF:

0.00

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

Bravo

AF:

0.00000756

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

Sep 27, 2024

The c.178A>T (p.R60W) alteration is located in exon 1 (coding exon 1) of the MDFIC gene. This alteration results from a A to T substitution at nucleotide position 178, causing the arginine (R) at amino acid position 60 to be replaced by a tryptophan (W). 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

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.55

T;T

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.67

PROVEAN

Benign

0.66

N;.

REVEL

Benign

0.021

Sift

Uncertain

0.014

D;.

Sift4G

Uncertain

0.011

D;D

Vest4

0.23

MutPred

0.35

Loss of methylation at R55 (P = 0.032);Loss of methylation at R55 (P = 0.032);

MVP

0.22

ClinPred

0.95

GERP RS

3.2

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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