Genetic Variant ENST00000393486:c.-184G>C (chr7-114922560-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The ENST00000393486.6(MDFIC):c.-184G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,117,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

MDFIC
ENST00000393486.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.223

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06861013).

BP6

Variant 7-114922560-G-C is Benign according to our data. Variant chr7-114922560-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3871432.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393486.6. 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.-184G>C		5_prime_UTR	Exon 1 of 5	NP_001159817.1	Q9P1T7-2
MDFIC	NM_199072.5		c.144G>C	p.Arg48Ser	missense	Exon 1 of 5	NP_951038.1	Q9P1T7-1
MDFIC	NM_001166346.1		c.144G>C	p.Arg48Ser	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.-184G>C	5_prime_UTR	Exon 1 of 5	ENSP00000377126.1	Q9P1T7-2
MDFIC	ENST00000963682.1		c.-184G>C	5_prime_UTR	Exon 1 of 6	ENSP00000633741.1
MDFIC	ENST00000904588.1		c.-181G>C	5_prime_UTR	Exon 1 of 5	ENSP00000574647.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000358

AC:

AN:

1117082

Hom.:

Cov.:

AF XY:

0.00000377

AC XY:

AN XY:

530450

show subpopulations

African (AFR)

AF:

0.000126

AC:

AN:

23828

American (AMR)

AF:

0.00

AC:

AN:

9406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14644

East Asian (EAS)

AF:

0.00

AC:

AN:

27866

South Asian (SAS)

AF:

0.00

AC:

AN:

22938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3688

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

932932

Other (OTH)

AF:

0.00

AC:

AN:

44700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.074

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.45

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.19

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.86

PhyloP100

0.22

PROVEAN

Benign

0.21

REVEL

Benign

0.031

Sift

Benign

0.88

Sift4G

Benign

0.61

Vest4

0.16

MutPred

0.27

Gain of phosphorylation at R48 (P = 0.0053)

MVP

0.030

ClinPred

0.25

GERP RS

1.5

PromoterAI

0.011

Neutral

(source)

gMVP

0.071

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

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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