NM_001166345.3:c.-184G>C

Variant names:

• chr7-114922560-G-C
• rs752906773
• NM_001166345.3:c.-184G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001166345.3(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 NM_001166345.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.223
• 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: 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: 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.-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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 32

GnomAD4 exome AF: 0.00000358 AC: 4 AN: 1117082 Hom.: 0 Cov.: 31 AF XY: 0.00000377 AC XY: 2 AN XY: 530450

African (AFR) AF: 0.000126 AC: 3 AN: 23828

American (AMR) AF: 0.00 AC: 0 AN: 9406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14644

East Asian (EAS) AF: 0.00 AC: 0 AN: 27866

South Asian (SAS) AF: 0.00 AC: 0 AN: 22938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3688

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 932932

Other (OTH) AF: 0.00 AC: 0 AN: 44700

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
PhyloP100		0.22
PromoterAI		0.011	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs752906773; hg19: chr7-114562615;