7-114942347-T-A

Position:

chr7-114942347-T-A

Variant summary

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

The NM_001166345.3(MDFIC):c.167T>A(p.Met56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 1,607,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

MDFIC
NM_001166345.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.220

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=0.009070665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDFIC	NM_001166345.3 linkuse as main transcript	c.167T>A	p.Met56Lys	missense_variant	3/5	ENST00000393486.6	NP_001159817.1	Q9P1T7-2
MDFIC	NM_199072.5 linkuse as main transcript	c.494T>A	p.Met165Lys	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.167T>A	p.Met56Lys	missense_variant	3/5	1	NM_001166345.3	ENSP00000377126.1	Q9P1T7-2
MDFIC	ENST00000498196.1 linkuse as main transcript	c.2T>A	p.Met1?	start_lost	2/4	4		ENSP00000418337.1	C9J784
MDFIC	ENST00000427207.5 linkuse as main transcript	c.125T>A	p.Met42Lys	missense_variant	2/4	3		ENSP00000392098.1	H7BZY3
MDFIC	ENST00000431629.5 linkuse as main transcript	n.137T>A		non_coding_transcript_exon_variant	2/5	5		ENSP00000416668.1	H7C4B9

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00512

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000334

AC:

AN:

248296

Hom.:

AF XY:

0.000238

AC XY:

AN XY:

134184

show subpopulations

Gnomad AFR exome

AF:

0.00458

Gnomad AMR exome

AF:

0.000206

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:

0.00000889

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000132

AC:

192

AN:

1454722

Hom.:

Cov.:

AF XY:

0.0000953

AC XY:

AN XY:

723758

show subpopulations

Gnomad4 AFR exome

AF:

0.00478

Gnomad4 AMR exome

AF:

0.000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.000316

GnomAD4 genome

AF:

0.00146

AC:

223

AN:

152296

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00510

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.00142

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000461

AC:

Asia WGS

AF:

0.000289

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.494T>A (p.M165K) alteration is located in exon 3 (coding exon 3) of the MDFIC gene. This alteration results from a T to A substitution at nucleotide position 494, causing the methionine (M) at amino acid position 165 to be replaced by a lysine (K). 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

0.087

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Benign

0.67

DANN

Benign

0.93

DEOGEN2

Benign

0.095

.;T;.;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.32

T;T;T;T;D

M_CAP

Benign

0.0017

MetaRNN

Benign

0.0051

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

.;N;.;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

N;N;.;N;N

REVEL

Benign

0.27

Sift

Benign

0.14

T;T;.;T;D

Sift4G

Benign

0.92

T;T;T;T;D

Polyphen

0.0

.;B;.;.;.

Vest4

0.48

MVP

0.19

ClinPred

0.0029

GERP RS

0.66

Varity_R

0.15

gMVP

0.22

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