rs764512112

Variant names:

• chr7-114922570-T-C
• rs764512112
• NM_001166345.3:c.-174T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-114922570-T-C
• chr7-114922570-T-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• 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=0.11499119).

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

Sel.	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 32

GnomAD2 exomes AF: 0.00 AC: 0 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: 2 AN: 1116736 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 530106

African (AFR) AF: 0.00 AC: 0 AN: 23798

American (AMR) AF: 0.00 AC: 0 AN: 9416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14638

East Asian (EAS) AF: 0.00 AC: 0 AN: 27822

South Asian (SAS) AF: 0.00 AC: 0 AN: 22994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3872

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 932224

Other (OTH) AF: 0.0000447 AC: 2 AN: 44740

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000687 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Pathogenic	0.84
PhyloP100		1.3
PromoterAI		0.31	Neutral
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

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

Other links and lift over

dbSNP: rs764512112; hg19: chr7-114562625;