chr7-114923070-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001166345.3(MDFIC):c.37G>T(p.Val13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000427 in 1,403,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

MDFIC
NM_001166345.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

lymphatic malformation 12
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

MDFIC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13156608).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166345.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MDFIC	NM_001166345.3	MANE Select	c.37G>T	p.Val13Leu	missense	Exon 2 of 5	NP_001159817.1	Q9P1T7-2
MDFIC	NM_199072.5		c.364G>T	p.Val122Leu	missense	Exon 2 of 5	NP_951038.1	Q9P1T7-1
MDFIC	NM_001166346.1		c.364G>T	p.Val122Leu	missense	Exon 2 of 3	NP_001159818.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MDFIC	ENST00000393486.6	TSL:1 MANE Select	c.37G>T	p.Val13Leu	missense	Exon 2 of 5	ENSP00000377126.1	Q9P1T7-2
MDFIC	ENST00000423503.1	TSL:1	c.37G>T	p.Val13Leu	missense	Exon 1 of 2	ENSP00000401623.1	C9J104
MDFIC	ENST00000963682.1		c.37G>T	p.Val13Leu	missense	Exon 2 of 6	ENSP00000633741.1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150740

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000227

AC:

AN:

44036

AF XY:

0.0000389

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000169

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000399

AC:

AN:

1253186

Hom.:

Cov.:

AF XY:

0.00000812

AC XY:

AN XY:

616126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23878

American (AMR)

AF:

0.000129

AC:

AN:

15460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18518

East Asian (EAS)

AF:

0.00

AC:

AN:

26362

South Asian (SAS)

AF:

0.00

AC:

AN:

62678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3486

European-Non Finnish (NFE)

AF:

0.00000198

AC:

AN:

1012332

Other (OTH)

AF:

0.0000198

AC:

AN:

50460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73596

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41252

American (AMR)

AF:

0.00

AC:

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67666

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.081

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.51

M_CAP

Benign

0.0036

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

1.7

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.43

REVEL

Benign

0.072

Sift

Benign

0.31

Sift4G

Benign

0.30

Polyphen

0.023

Vest4

0.061

MutPred

0.19

Gain of sheet (P = 0.0149)

MVP

0.29

ClinPred

0.079

GERP RS

3.5

PromoterAI

0.028

Neutral

(source)

Varity_R

0.050

gMVP

0.080

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over