dbSNP rs764512112: MDFIC:c.-174T>C (chr7-114922570-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_199072.5(MDFIC):c.154T>C(p.Phe52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000179 in 1,116,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

MDFIC
NM_199072.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

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=0.11499119).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199072.5. 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.-174T>C		5_prime_UTR	Exon 1 of 5	NP_001159817.1	Q9P1T7-2
MDFIC	NM_199072.5		c.154T>C	p.Phe52Leu	missense	Exon 1 of 5	NP_951038.1	Q9P1T7-1
MDFIC	NM_001166346.1		c.154T>C	p.Phe52Leu	missense	Exon 1 of 3	NP_001159818.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MDFIC	ENST00000393486.6	TSL:1 MANE Select	c.-174T>C	5_prime_UTR	Exon 1 of 5	ENSP00000377126.1	Q9P1T7-2
MDFIC	ENST00000963682.1		c.-174T>C	5_prime_UTR	Exon 1 of 6	ENSP00000633741.1
MDFIC	ENST00000904588.1		c.-171T>C	5_prime_UTR	Exon 1 of 5	ENSP00000574647.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

30382

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000179

AC:

AN:

1116736

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

530106

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23798

American (AMR)

AF:

0.00

AC:

AN:

9416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14638

East Asian (EAS)

AF:

0.00

AC:

AN:

27822

South Asian (SAS)

AF:

0.00

AC:

AN:

22994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3872

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

932224

Other (OTH)

AF:

0.0000447

AC:

AN:

44740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

Cov.:

Alfa

AF:

0.0000687

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000969

AC:

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

Pathogenic

0.84

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.26

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.99

PhyloP100

1.3

PROVEAN

Benign

-0.32

REVEL

Benign

0.048

Sift

Benign

0.065

Sift4G

Benign

0.46

Vest4

0.30

MutPred

0.16

Loss of methylation at K56 (P = 0.0746)

MVP

0.040

ClinPred

0.70

GERP RS

2.2

PromoterAI

0.31

Neutral

(source)

gMVP

0.085

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over