7-114923070-G-C

Variant names:

• chr7-114923070-G-C
• rs1263865542
• NM_001166345.3:c.37G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166345.3(MDFIC):​c.37G>C​(p.Val13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000798 in 1,253,184 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: MDFIC NM_001166345.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 0 publications found

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

ACMG classification

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=0.14027467).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.98e-7 AC: 1 AN: 1253184 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 616124

African (AFR) AF: 0.00 AC: 0 AN: 23878

American (AMR) AF: 0.00 AC: 0 AN: 15460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18518

East Asian (EAS) AF: 0.00 AC: 0 AN: 26362

South Asian (SAS) AF: 0.00 AC: 0 AN: 62676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3486

European-Non Finnish (NFE) AF: 9.88e-7 AC: 1 AN: 1012332

Other (OTH) AF: 0.00 AC: 0 AN: 50460

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.7
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.072
Sift	Benign	0.31	T
Sift4G	Benign	0.30	T
Polyphen		0.023	B
Vest4		0.061
MutPred		0.19		Gain of sheet (P = 0.0149)
MVP		0.29
ClinPred		0.15	T
GERP RS		3.5
PromoterAI		0.0030	Neutral
Varity_R		0.050
gMVP		0.080
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs1263865542; hg19: chr7-114563125;